CIRM Stem Cell Research Updates

Genomics and stem cell research give patient her life back

2012-01-27T09:49:00.000-08:00

Sandra Dillon and her fiancé at the CIRM governing board meeting. Thanks to board member Leeza Gibbons for the photo.

Todd Dubnicoff is CIRM’s videographer and video editor

At 28, Sandra Dillon was the picture of healthy living. She ran every day, ate healthy, didn’t smoke and recycled. But she had been bothered by a bump under her rib cage and after numerous tests, her doctors came back with very bad news: she had myelofibrosis, a life-threatening blood disorder that can lead to acute leukemia. No cure existed and no match for a bone marrow transplant was found. The only course of treatment was to try to manage her symptoms as she got sicker. Basically, there wasn’t much hope.

That was eight years ago. Flash forward to last week when Dillon spoke at the CIRM Governing Board’s Spotlight on Disease seminar (watch that video on our website or on our YouTube Channel CIRMTV) to happily report a more hopeful prognosis now that she’s participating in a clinical trial that targets cancer stem cells:

I’ve been on this trial for almost three months and my spleen is getting smaller…This is after eight years…of perpetual pain like I was stuck at the top of a mountain where there wasn’t enough air and I couldn’t acclimate…I felt exhausted constantly and now I have energy.

Dillon’s story provides a glimpse into a future of personalized medicine in which genomics, the study of genes and their function, is applied to pinpoint specific treatments for patients. Catriona Jamieson, Sandra’s physician and director for stem cell research at the UCSD Moores Cancer Center, spoke about the research, funded in part by CIRM, which led to the clinical trial. Using patient samples and leukemia stem cells, Jamieson’s team identified abnormal gene activity responsible for the cancer progression. A specific small molecule known to inhibit this mutant gene activity halted the disease.

Craig Venter, a leading expert in genomics and president of the J. Craig Institute, also spoke at the Spotlight and described personalized medicine this way:

Knowing your genetic code, knowing your genetic variation is part of the future of medicine and part of determining whether you’re going to be treatable by existing drugs.

Application of genomics will be essential for developing stem cell therapies in addition to drug development based on lessons learned from stem cells in the lab. Both Venter and Jamieson point out that merely growing stem cells in the lab introduces changes in their genetic code. These changes can lead to genomic instability, which is associated with cancer. So it will be very important to understand these changes, why they happen, and how to prevent or repair them. Venter stressed this point with a prediction:

I’ll go as far to say that there will be no clinical stem cell application without understanding the genomics and the genetic variation that takes place to ensure we don’t do more harm than good.

The importance of genomics is not lost on the CIRM governing board. Later in the afternoon after the Spotlight, the board approved a $40 million CIRM Genomics Initiative to give California researchers the opportunity to access genomics tools to better understand the stem cells they are working with and to help advance those cells toward therapies for patients. (We blogged about that initiative here.)

Sandra Dillon also appreciates the importance of genomics. Before she began her clinical trial, she was in too much pain and too exhausted to go out with friends at night. Now she plans to stay out all night with her fiancé during their wedding in March.

This page has more information about the work of CIRM grantees developing therapies for leukemia.

T.D.

Alzheimer's disease in a dish provides hope, avenue to therapies

2012-01-25T15:12:00.000-08:00

In Lawrence Goldstein’s lab at the new Sanford Consortium building in San Diego, a series of lab dishes hold cells that could unlock some of the mysteries of Alzheimer’s disease.

These cells are neurons made from the skin of people who have the disease. Goldstein and his team reprogrammed those skin cells into embryonic-like iPS cells, then matured those into nerve cells. The nerve cells in the dish show many of the same abnormalities scientists have come to recognize as hallmarks of the disease – higher levels of some proteins that form tangled masses and plaques in the brain.

The work was published today in Nature and is based on funding from CIRM awards to Goldstein and his co-authors Martin Marsala, Fred H. Gage and first author Mason Israel.

In the past, those tangles and plaques have only been seen in biopsies taken from people with the disease after they have died, providing a snapshot of the ravages caused by a lifetime of the disease. These cells and their unusual proteins in the lab dish represent the first time scientists have been able to study how the human nerve cells first start to go awry, and could provide clues to help guide new treatments for the disease. Currently there are no drugs to treat the estimated 30 million people worldwide who have the disease.

A story in Nature describes the work:

Scientists aiming to learn the causes of Alzheimer’s have looked to brain biopsies of patients after they die, blood tests and animals as diverse as fruitflies and fish. Until recently, it has not been possible to probe the neurons of Alzheimer’s patients before they show symptoms.

“By the time you can see dementia in a person, their brain cells have been behaving in an abnormal way for years, perhaps decades or longer,” says Larry Goldstein, a neuroscientist at the University of California, San Diego, who led the study published online today in Nature.

The group started with skin cells from four people with Alzheimer’s disease, two with the disease in their family and two who did not have the disease in their family. The idea is that the disease runs in families due to a single genetic change that makes the cells malfunction. The people who don’t have the disease in their family might have developed the disease due to genetic or environmental causes or other reasons. Having both sets of cells could allow the researchers to tease apart how the disease originates in people with known mutations versus through other causes.

These kinds of disease-in-a-dish studies have been carried out for a few different diseases in recent years, including schizophrenia, Parkinson’s disease and forms of autism, among others. In each case, one goal is to use the cells to test for drugs that can eradicate symptoms. If a drug can return an Alzheimer’s-like cell in a lab dish to a normal state, it might also help treat a person with the disease.

Nature writes:

But the hope is that such cells will help scientists to develop new drugs and match them to individual patients based on how their reprogrammed brain cells respond. Reprogrammed cells could even be used to diagnose people with Alzheimer’s decades before they show symptoms, Goldstein says. This would be of little use without proven therapies, but early diagnoses could help scientists select patients for clinical trials, he says.

“We’re in a terrible situation with a very common, devastating disease. It’s devastating financially and it’s devastating emotionally to the families who have to cope with it, and we have nothing to give patients that will work,” Goldstein says.

Finding a treatment for disabling conditions like Alzheimer’s disease was one of the driving reasons for the passage of proposition 71, which created CIRM. Leeza Gibbons has served on our board as a patient advocate for Alzheimer’s disease and is one of the patient advocate board members who help keep the board’s focus on therapies and patients who need them. Her mother had Alzheimer’s disease. She went on to found Leeza's Place to support the caregivers of people with Alzheimer's disease and other conditions.

CIRM has funded $11 million in awards focusing on Alzheimer’s disease. You can see a list of those awards here.

CIRM did a video with Fred Gage, one of the co-authors on this paper, talking about the use of stem cells in modeling diseases:

A.A.

Israel MA, Yuan SH, Bardy C, Reyna SM, Mu Y, Herrera C, Hefferan MP, Van Gorp S, Nazor KL, Boscolo FS, Carson CT, Laurent LC, Marsala M, Gage FH, Remes AM, Koo EH, & Goldstein LS (2012). Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells. Nature PMID: 22278060

Early results from two embryonic stem cell-based trials show promise

2012-01-24T14:01:00.000-08:00

Yesterday, the company Advanced Cell Technology announced that two people in their clinical trials testing an embryonic stem cell-based therapy for forms of blindness is not only safe so far, but shows tentative early signs of restoring some vision in two patients. The work was published online January 23 in the journal The Lancet.

Of the two women discussed in the paper one had macular degeneration, the leading cause of blindness, and the other had the most common form of blindness in children, called Stargardt’s macular dystrophy. Both were participating in phase 1 trials testing cells derived from embryonic stem cells as a possible treatment for their blindness. All phase 1 trials are primarily designed to make sure a therapy is safe, but the researchers do also look for signs that the therapy might be effective. (We have more information about the phases of clinical trials on our website.)

The preliminary news that two women in these trials reported some improvements in vision warrants some cautious optimism. For those of us who have been following the field since the discovery of embryonic stem cells in 1998, this paper is a milestone. It’s the first published paper showing that—at least in this small number of patients for the first few months—the cells are safe.

However, two patients isn’t enough to show whether the therapy actually works. In fact, in a New York Times story Steven D. Schwartz, a professor of ophthalmalogy at UCLA's Jules Stein Eye Institute, who is leading the research, said there was evidence that at least one of the two patients might have experienced a placebo effect. Sorting out the real improvements from the placebos or short-term changes takes time, which is why clinical trials are set up to follow patients for several years. Only after many more people receive injections of the cells and are followed for several years will we know that the cells were effective.

A story by NPR quoted Schwartz:

Schwartz and his colleagues stressed that the findings are extremely preliminary and it's far too early to know anything for sure. The patients could continue to improve, or their vision could deteriorate again, he said. Many more patients will be needed to be treated for far longer to know whether the therapy is really safe and responsible for any improvement.

"My job is to decrease suffering, and if we overstate this and raise hopes falsely and then it doesn't work out, it will hurt people rather than help them," Schwartz said.

The Stanford University medical blog has more commentary on this trial from law professor Hank Greely. He's been following the field of embryonic stem cell research since the beginning and says the news is, "at least, a little exciting – and in a field that saw its first approved clinical trial stopped two months ago, even a little exciting news is very welcome." You can read more on their blog.

These are the only two trials currently underway testing an embryonic stem cell-based therapy. Along with the rest of the stem cell community we’ll be watching the results, and following the additional trials that are expected to start in the next few years. It’s through clinical trials such as these that safe and effective stem cell-based therapies will eventually reach patients.

A.A.

CIRM and Scotland team up in stem cell research collaboration

2012-01-23T12:35:00.000-08:00

Last week CIRM and Scottish Development International, which promotes science research and economic development in Scotland, signed an agreement to collaborate on stem cell research.

This agreement marks 12th international funding agency to sign a collaborative agreement with CIRM. The agency also has agreements with federal and state funding agencies and foundations within in the U.S.

These agreements serve a valuable role in accelerating stem cell therapies. As a state agency, CIRM can only fund research within California. In some cases, however, those California scientists benefit from the expertise of colleagues who reside outside the state. With the collaborative agreements in place, the California scientists can find the best partners for developing new therapies. CIRM funds the California scientists and the collaborative funder supports the research in their jurisdiction.

We have a page on our website that lists the funding agreements and describes the process. You can also see all CIRM awards that include a collaborative funder. Altogether, these arrangements have leveraged more than $60 million dollars for stem cell research internationally.

The press release quotes Danny Cusick, president of the Americas for the Scottish Development International.

“We are committed to supporting Scottish-based companies to work with California scientists and businesses to further boost Scotland’s profile as the primary location to undertake clinical trials, create new opportunities for California companies to (invest) in Scotland and increase customers for our rapidly growing stem cell supply chain.”

CIRM president Alan Trounson talks about the collaborative funding agreements as creating a 24-hour-per-day stem cell workforce. “With our partners located around the world, the sun never sets on CIRM teams working toward new therapies.”

A.A.

Genomics initiative creates California infrastructure for speeding stem cell research

2012-01-20T09:24:00.000-08:00

Earlier this week the CIRM governing board approved $40 million to fund a stem cell genomics initiative (here’s our press release). Stay with me here—this is actually really cool stuff, and crucial if we’re going to be able to generate the kinds of stem cell-based therapies patients and their families are waiting for.

Genomics is the study of all the DNA in a cell. That includes the actual sequence of the DNA, which is the same in all the cells of a person’s body, as well as the molecular decorations hanging on to the DNA. Those decorations, collectively called epigenetics, can determine the behavior of the genes such as which are active or inactive in a given cell. It’s epigenetics that can control why, if a hair cell and a liver cell have the same DNA, one makes hair and the other makes liver enzymes. Those epigenetic changes are also responsible for why an embryonic stem cell behaves one way, and the neuron it can mature into behaves differently.

Genomics also reveals molecules called RNA that are coded by the DNA and controlled by epigenetics. RNA can reveal a cell’s status as it differs from cell to cell depending on what kind of cell it is and whether the cell is healthy, diseased, or in damaged tissue.

Here are a few examples of how genomics is important for stem cell research. Let’s say a team wants to create reprogrammed iPS cells from the skin of a person with a genetic disease like Parkinson’s disease. First, those researchers need to know whether the process of reprogramming that skin cell into an embryonic-like cell altered the DNA. There’s a lot of controversy over whether iPS cells truly mimic embryonic stem cells (which we blogged about here), and knowing more about the genomics of iPS cells will help develop the best methods for creating those cells. This will also help the CIRM’s cell banking initiative, which will fund researchers to create and bank iPS cells in addition to banking embryonic stem cells for widespread distribution to stem cell researchers. With access to genomics resources we can be sure those iPS cells are genetically normal and consistent.

If we want to study and treat Parkinson’s disease, the next step would be to mature those iPS cells into dopaminergic neurons ,the type of neuron that goes awry in the disease. Genomic analysis will tell researchers whether the dopaminergic neurons are different when they are generated from skin cells of people without the disease and from people with the disease. Those differences could reveal a lot about what causes the disease in the first place. The information can also be used to screen for drugs that make neurons from people with the disease more like their normal, non-diseased counterparts.

The information is incredibly powerful. It’s also growing much, much cheaper. In the past it was too expensive and time-consuming to routinely carry out genomic analysis. With those costs coming down, and the process speeding up, it’s a good time to invest in genomics resources that would be available to California researchers.

In a paper published this month in Nature Biotechnology, CIRM president Alan Trounson with Natalie DeWitt and Michael Yaffe of the science office wrote:

For California to take a firm and lasting grip on leadership in stem-cell research—and, as stated in Proposition 71, “advance the biotech industry in California to world leadership as an economic engine for California's future”—its scientists must have access to these technologies and moreover create a coordinated international enterprise to maximize the reach and impact of stem cell genomics. Genomics is creating a sea change in biomedical research and medicine, and accordingly, the California Institute for Regenerative Medicine (CIRM; San Francisco) can create a process through which stem-cell research can participate and even provide leadership in a new era of medicine… With judicious expenditure of CIRM funds, it should be possible to use existing resources to rapidly and efficiently build an effective stem-cell genomics infrastructure that will be unique in the world, thus positioning California as a leader in this critical area of basic and translational research while genomic technologies build steam in the next five years.

The group also points out that although several research institutes in other states provide comprehensive genomics centers, none exist in California. That’s despite the fact that several of the major companies that make genomics tools are located in the state.

The requests for applications (RFA) for this initiative will be posted on this page of the CIRM website this spring. If you haven’t already signed up, here’s a link where you can sign up to get an email alert whenever CIRM posts a new RFA.

A.A.

Dewitt ND, Yaffe MP, & Trounson A (2012). Building stem-cell genomics in California and beyond. Nature biotechnology, 30 (1), 20-5 PMID: 22231086

National war on Alzheimer's disease brings hope to patients and caregivers

2012-01-19T13:02:00.000-08:00

In Washington D.C. this week, researchers and patient advocates are giving feedback on what will become the nation’s war on Alzheimer’s disease, which aims to prevent and treat the disease by 2025.

The Department of Health and Human Services released a draft Framework for the National Plan to Address Alzheimer’s Disease on January 9. After receiving feedback, the final draft is expected late January or early February, according to a story in U.S.A. Today. That story goes on to quote Carol Blackwell, whose husband has the disease and whose family has experienced the financial burden of high medical costs and reduced income:

"My mother-in-law has been in a facility for 15 years," Carol Blackwell says. "In 2005, after her husband died … she'd used up all her money (for care), and Bob had to file for Medicaid for her. She's been living at the government's expense since then. We have to prevent those costs down the road."

There are 5 million people living in the U.S. with Alzheimer’s disease, and 15 million people estimated to be providing care for family members with the disease. The emotional and economic toll from the disease can be devastating. CIRM board member Leeza Gibbons cared for her own mother, then went on to write the award-winning book “Take Your Oxygen First” to help other caregivers care for themselves. She also started Leeza’s Place to provide support for caregivers. She writes:

Life doesn't always go as planned. The people we love get sick, they get diseases and we often feel helpless to do anything about it. When you are a husband or wife, son or daughter, brother, sister or friend who takes care of someone in your family or someone you love, chances are you need help too. That's where we come in...

Leeza Gibbons and other patient advocate board members keep CIRM’s eye on the end goal of accelerating new therapies. CIRM has funded eight projects with a focus on Alzheimer’s disease, worth a total of $11 million. This page describes the CIRM-funded projects and includes a list of grants and other resources describing stem cell-based approaches to treating the disease.

The U.S. draft framework came out during what is also Canada’s Alzheimer’s Disease Awareness Month. The Canadian Minister of Health Leona Aglukkaq posted a message about the month:

Alzheimer's disease, or related dementia, affects an estimated 500,000 Canadians, and statistics predict that this number will double within a generation. Fortunately, for every person living with Alzheimer's disease, there are also many family members and friends providing care and support.

A major national push to treat Alzheimer’s disease will help all those people with the disease and their family members avoid the associated heartache and economic loss.

This video discusses advances in a stem cell-based therapy for Alzheimer’s by a CIRM funded team at University of California, Irvine:

A.A.

Ataxia patients and family members learn about stem cell progress

2012-01-17T10:32:00.000-08:00

I was scheduled to give a talk to the Northern California Ataxia Support Group Saturday, just 15 minutes before the Fortyniners were about to begin their first playoff game in years. A colleague picked me up at the local BART train station and we drove up to a mostly empty parking lot at the church where the meeting was supposed to take place. We wandered through the empty upper halls and as we approached a stairwell started to hear voices. Turned out the church has a second parking lot on the back side that opens to a lower level—key for the 30 some individuals gathered that day, many mobility challenged, who were gathered around two long tables.

For them the chance to get together to share information about their poorly understood mix of diseases and to hear about the promise of stem cells was more important than the football game some commentators were calling historic. Ataxia refers to an assortment of conditions, some inherited and some sporadic that all involve the nervous system with primary symptoms related to gait and mobility. They also have the commonality of being relatively poorly understood and ineffectively treated with current standards of care.

I did not come prepared to offer them news that we were close to clinical trials using stem cells to treat their diseases. We are not. But I was armed with news of two grants CIRM has funded that have already improved our understanding of a couple of ataxias and perhaps opened up the opportunity to find more effective traditional small molecule drugs. CIRM has funded two teams, one at UCLA and one at Scripps, that are both using cell samples form ataxia patients to create reprogrammed stem cells, called induced Pluripotent Stem Cells (iPSC), to create “disease-in-a-dish” models.

One team has already published a journal article on its model of Friedreich’s Ataxia (Cell Stem Cell, November 5, 2010), which offered a better explanation of the mutation involved in the disease, offering a point of departure for addressing the mutation. The other team is working on a form of ataxia that goes by the acronym A-T that is a particularly debilitating form that strikes children. It was known to be caused by a type of mutation called a “nonsense” coding error in the DNA. The team had previously developed several compounds that would allow the patient’s cellular machinery to read through the nonsense coding and go ahead and produce the protein that is missing in these kids. But there is no animal model of these diseases so there was no way to do the pre-clinical testing required to put the compounds in clinical trials in humans. Now they will have a model, cells from patients in a dish. So, there is hope one of those compounds can be shown to be worthy of a clinical trial.

This meeting was one of many that CIRM holds with patient advocacy groups in California as a way of ensuring that those groups who have the most at stake know about progress being made in developing therapies for the diseases that matter to them. These groups played a critical role in the creation of CIRM, and continue to have a loud voice in pushing CIRM to maintain our focus on new therapies. CIRM also keeps advocacy at the core of its mission through input from the 10 patient advocates who serve on our board. Our board member Jeff Sheehy wrote a blog entry on the importance of patient advocates in steering funding agencies like CIRM.

My audience and I had a good conversation about the long-term hope stem cell research provides. They seemed excited by this hope, but also exhibited a gentle patience, probably a brand of patience that can only be instilled by years of living with an intractable disease.

I got home in time to see the final few incredible minutes of the nail-biting football game and to hear our neighborhood explode with fire crackers and honking horns, but I did not regret one bit missing those first three quarters of play. That game ending was just the icing on a very satisfying cake.

DG

Ku S, Soragni E, Campau E, Thomas EA, Altun G, Laurent LC, Loring JF, Napierala M, & Gottesfeld JM (2010). Friedreich's ataxia induced pluripotent stem cells model intergenerational GAA⋅TTC triplet repeat instability. Cell stem cell, 7 (5), 631-7 PMID: 21040903

Second synthetic trachea transplant shows promise of tissue engineering, regenerative medicine

2012-01-13T13:54:00.000-08:00

Today brought the news of a second transplanted synthetic trachea seeded with a person’s own stem cells. As with the first such transplant, carried out last June, this one replaced the trachea in a person whose own windpipe had been damaged by cancer.

The timing on this story is exciting for us at CIRM. We’re currently hosting a group of tissue engineering experts—including Martin Birchall who was part of the team that carried out the first tissue engineered tracheal transplant—to help the agency understand how we could move the field forward. Other people at this workshop are working on projects to develop intestines, repair hearts, and generate synthetic polymers to help keep stem cells intact and alive during a transplant.

CIRM president Alan Trounson was quoted in the New York Times story about the transplant. He said that he was worried about the patient’s body responding to the foreign object and encapsulating it:

While he described Dr. Macchiarini’s work as “terrific,” he said he was not sure how long such a transplant could be expected to last.

“It looks very functional at this stage,” Dr. Trounson said. “But there’s going to be a reaction of some kind.” More work will probably be needed to develop scaffold materials that are optimized to reduce the response,” he added. This concern about preventing the body from rejecting engineered structures is one that has come up regularly among the experts CIRM is meeting with today. Another major topic of discussion is how to prove to the Food and Drug Administration that engineered structures are safe for use in humans.

In September CIRM held a webinar on scaffolding that included speakers from the FDA. One goal of that webinar was to help inform researchers about the regulatory process for developing stem cell therapies based on engineered scaffolding, such as the trachea. We’re hoping that through these webinars and by speaking with experts in the field, CIRM can help bring this promising area of research to more patients. That webinar and the associated slides are available on our website.

A.A.

CIRM boosts industry outreach efforts in 2011, more to come

2012-01-12T10:16:00.000-08:00

Cynthia Schaffer is Contract Administrator and Compliance Officer at CIRM

As CIRM-funded teams move closer to clinical trials, we’re ramping up our engagement with the industry partners who are integral to the success of most future stem cell therapies. In my role supporting many of these endeavors I saw a significant uptick in 2011 in events and activities specifically focusing on these crucial industry groups.

For the second year in a row, CIRM organized webinars and roundtables with the FDA, industry and investigators from academia. These events focused on the challenges and/or roadblocks on the regulatory pathway to develop stem cell based therapies. Topics of these webinars included Imaging in May, Scaffolding in September and Immune Response in October.

Through our active engagement with the Alliance for Regenerative Medicine (ARM), CIRM sponsored the first ever regenerative medicine investor partnering event in November in conjunction with CONNECT and the Stem Cell Meeting on the Mesa. My colleague Elona Baum, CIRM General Counsel and Vice President of Business Development, was one of the primary organizers of this event, which was attended by more than 240 regenerative medicine professionals and featured 40 company presentations and a full day of panel discussions addressing key business topics. Participants came from across the regenerative medicine sector including big pharma, investors, leaders from Europe and Asia, therapeutic and platform companies, investigators and representatives from several prominent CIRM disease teams.

As part of the update to CIRM’s Strategic Plan, CIRM held four public meetings in October, two of which specifically targeted input from the for-profit sector of the Regenerative Medicine industry. The Strategic Plan update will be presented to the board at the upcoming governing board meeting January 17 in San Diego (location and audiocast details are available here).

At CIRM’s Grantee Meeting in September, 12 vendors from various for-profit companies who serve the regenerative medicine industry were able to exhibit their wares. This program was well received and we plan to incorporate this element again at our next CIRM Grantee Meeting in 2013.

In 2011 CIRM hosted two webinars on its new Disease Team Therapy RFA to help potential applicants understand CIRM’s expectations for their proposals and budgeting materials. These webinars append the 2010 Grant Writing webinar (archived on CIRM’s website) and similar curriculum is planned for 2012.

Also this year, CIRM allocated a significant $57 million to be invested in initiatives that will make the organization more flexible in seizing funding opportunities and partnering with industry (we blogged about those initiatives here). Baum said:

“We were very pleased with the Board’s approval in December of all three components of the Opportunity Fund: Bridge Funding ($12 million), External Innovation ($15 million) and the Strategic Partnership program ($30 million). We believe the Opportunity Fund and its components will give us increased flexibility in responding to opportunities that arise in the Regenerative Medicine industry.”

In addition to resources I link to here, I would specifically like to call your attention to the materials on Resources for Researchers page.

If you want to be alerted about upcoming industry events, you can sign up to receive notifications for all upcoming meetings here.

C.S.

CIRM-funded building at UC Irvine receives LEED Platinum certification

2012-01-10T11:05:00.000-08:00

Michelle Kim / University Communications

In May 2010 University of California Irvine opened their new stem cell building funded in part by CIRM. In addition to its state-of-the art research facilities designed to speed the development of stem cell therapies, the Sue & Bill Gross Hall also recently received LEED Platinum certification from the U.S. Green Building Council.

According to a press release from UCI:

Gross Hall scored points for such features as dimmable and occupancy-controlled lighting, use of energy-saving building materials, and mechanical systems that are 50 percent more efficient than required by California’s Title 24 energy code. The operable windows are tied into the heating and air-conditioning controls so that when a window is opened, mechanical ventilation of that room shuts off.

An $80 million, 100,000-square-foot structure, Gross Hall was designed to facilitate contact between patients in the first-floor clinic and rehabilitation center and stem cell researchers on the first, second and third floors. Labs are equipped with Aircuity technology that monitors indoor air quality and adjusts air-change rates based on contaminant levels.

UCI received $27 million from CIRM for the building and a $10 million from Sue & Bill Gross. The remaining funds came from donations and institutional commitments leveraged by CIRM's investment. This is one of the 12 buildings supported through CIRM's Major Facilities programs. The complete list of those buildings is available here. The 12 major facilities received $272 million from CIRM, with private donations and institutional investments bringing the project totals to more than $1 billion. An independent review of the impact of this investment for the state economy suggested that the projects would create 13,000 job years of employment and $100 million in tax revenue.

A.A.

60 Minutes highlights concerns about clinics marketing unverified stem cell treatments

2012-01-09T13:19:00.000-08:00

Last night, 60 minutes aired a report describing the dangers of what has become known as stem cell tourism – people traveling to other countries to receive unverified “treatments”. You can watch the episode here. In the story, they spoke with Gary Susser, whose son Adam has cerebral palsy. Susser and his wife took Adam to a doctor in Mexico, who injected Adam with stem cells but provided no evidence that the injections would be effective. They were not. In the story Susser said:

"I see how people are preyed upon by hucksters and charlatans. And people who have a special child don't need any more expense, don't need any more heartache, and don't need any more false promises. They need the truth and they need hope."

Susser and his wife worked with 60 minutes to investigate a clinic in Ecuador that advertises therapies for 70 incurable diseases including cerebral palsy.

This trend of overseas clinics offering “modern day miracles,” as the Ecuadorian clinic’s website promises, is one that has concerned both CIRM and the International Society for Stem Cell Research (ISSCR). In 2010, when the ISSCR held its annual meeting in San Francisco, CIRM and ISSCR co-hosted a symposium about these clinics and the concerns they raise. A video of that session is available on the CIRM website.

At that same meeting, then-head of the ISSCR Irv Weissman used his opening address to both tout a new ISSCR website designed to help people identify clinics offering true therapies (A Closer Look at Stem Cell Treatments), and also discussed what he saw as the dangers of stem cell tourism. In countries without strong oversight bodies such as the Food and Drug Administration in the U.S., clinics can make claims about potential therapies without backing those claims up with any proof that the procedure will work or even be safe. An investigational treatment offered for sale, which is what these clinics described on 60 minutes are offering, is not the same as a clinical trial, which would show whether the new treatments are safe and effective.

In the 60 minutes piece, the clinic under investigation had proposed injecting cells that, when scrutinized by Dr. Joanne Kurtzberg of Duke University, turned out to be disintegrating. She said:

"There are huge dangers if you injected that into someone's blood or spinal fluid because all these little fragments and debris would get trapped somewhere in the blood stream and could cause a stroke, or in the brain could cause an inflammatory reaction."

Weissman spoke with Stanford’s Krista Conger, who wrote a story on the topic for the magazine Stanford Medicine. In it Weissman said:

“This is a new field. We are learning what kinds of stem cells can regenerate which kinds of failing organs. But we always remember that our first goal is to do no harm. That’s why we begin our tests in animals before moving into early phase clinical trials in humans, and at every stage we verify the solidity and reproducibility of the science and that the investigators have no potential commercial or personal conflicts of interest that could influence the outcome of the trials. Any attempt to commercialize unproven treatments in the absence of independent or regulatory oversight endangers not only the lives of those who receive the treatments, but also the entire field of regenerative medicine.”

Conger also quoted CIRM grantee Jeanne Loring, director of the Center for Regenerative Medicine at the Scripps Research Institute in La Jolla, Calif.:

“When we report something good about stem cells, it gets picked up in the media, or in a blog that patients read. It gives them more ammunition to say that the FDA is stupid for denying access to treatments that seem like they should work.”

At CIRM, we know how frustrating the timeline of developing new therapies can be. We also have friends and family members with diseases desperately in need of new therapies. That sense of urgency is constantly reiterated by our board members, ten of whom serve on the board as patient advocates. (Our board member Jeff Sheehy has blogged about the role of advocates in accelerating the pace of new therapies.)

That’s why we’re working with industry, pushing teams to collaborate, and engaging the FDA to try to speed that timeline and get new therapies to the patients who need them. Today we have 43 projects in various stages of working their way to the clinic, with several we hope to see enter clinical trials in the next few years. You can read more about our projects in development and the steps along the path to a new therapy on our website.

If people are considering clinics outside the U.S., please do read the ISSCR web page. They have a good list of qualifications to look for in identifying clinics that are being truthful about what they offer rather than simply peddling hope. Included in what they suggest people look for is oversight of investigational treatments to be sure the physicians are qualified, the investigational treatment is prepared appropriately, and that the risks and potential benefits are accurately and clearly explained. People should also look for published records showing results from clinical trials. CIRM also has a page about stem cell tourism and what we are doing to try to speed the timeline to new therapies.

A.A.

CIRM's 1,000th published paper targets Huntington's disease

2012-01-05T08:48:00.000-08:00

CIRM recently realized a noteworthy milestone with the publication of the 1,000th CIRM-funded paper in early December (here is a link to that paper). This is exciting to me personally because one of my first assignments when I joined CIRM three years ago was to develop (in collaboration with my Science Office colleague Rahul Thakar) a system and database for tracking CIRM-funded publications. At that point, there were only around 100 CIRM-funded papers, mostly from training grants, which were the first grants CIRM awarded in the spring of 2006. Watching the database grow and the publication rate accelerate has been exciting because these papers describe real progress that CIRM grantees are making in understanding stem cell biology, mechanisms of human disease and advancing stem cell-based therapies to the clinic.

The 1,000th paper itself is a great example of this progress. It was published in the journal Molecular & Cellular Neuroscience by Drs. Scott Olson, Jan Nolta and colleagues at UC Davis with the title “Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin”. The fact that the thousandth journal article comes from Jan Nolta's lab has added significance given that she was just yesterday named editor of one of the leading specialty journals in the field Stem Cells.

The promising research described in this paper was funded in large part by a CIRM Early Translational grant to Nolta, which has the goal of developing a combination cell and gene therapy candidate to treat Huntington’s Disease, a devastating neurological disease for which there is no effective treatment. Among those who have suffered and died from Huntington’s is one of my favorite songwriters, Woody Guthrie, whose 100th birthday will be celebrated in July. There's more information about Huntington's disease and awards we've funded available on our website.

In Huntington’s Disease, a mutated form of a protein called huntingtin causes certain neurons in the brain to die. The goal of Nolta’s award is to use stem cells to disable the ability of those neurons to make the disease-causing protein. In their paper, Nolta and colleagues show that a type of stem cell found in the bone marrow called mesenchymal stem cells (MSCs) can be engineered to produce a molecule that inhibits the production of the mutated huntingtin protein. They show, in a petri dish, that this molecule is secreted by the stem cells, is taken up by nearby neuronal cells, and reduces the amount of the disease-causing protein produced by those cells. The next important step will be testing these engineered stem cells in an animal model of Huntington’s.

With over a thousand CIRM-funded publications come a lot of data and statistics that allow us to assess our programs and progress. Of the 1,009 CIRM-funded publications, 770 describe original research, 175 are literature reviews and 64 describe novel scientific methods. The top four RFAs by publication number are, not surprisingly, the four earliest in CIRM’s funding history: Training grants with 574 publications, New Faculty with 178, Comprehensive with 169 and SEED with 160. CIRM funding has resulted in an impressive number of papers in elite journals: 55 in Nature, 47 in Cell Stem Cell, 24 in Cell and 13 in Science. In total,298 CIRM-funded papers have been published in journals with impact factors greater than 10. There were 10 CIRM-funded publications in 2006, 68 in 2007, 151 in 2008, 224 in 2009, 261 in 2010, and 295 in 2011, so I predict that I’ll be back to blog about the 2,000th paper before the end of 2014!

Zachary Scheiner is a Science Officer at CIRM

Olson SD, Kambal A, Pollock K, Mitchell GM, Stewart H, Kalomoiris S, Cary W, Nacey C, Pepper K, & Nolta JA (2011). Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington's disease affected neuronal cells for reduction of huntingtin. Molecular and cellular neurosciences PMID: 22198539

Looking ahead to 2012

2012-01-04T13:28:00.000-08:00

Yesterday CIRM president Alan Trounson took a look back over his science picks from 2011. Today, we're looking ahead to what's in store in 2012.

First, anyone interested in participating in the 2012 board meetings should take a look at the governing board meeting schedule. That's available here. We'll be having seven meetings at locations throughout California. As always, you can see any scheduled subcommittee or working group meetings on this page and you can also sign up to receive email notifications whenever we post new agendas. That sign up is here.

Those meetings will be action-packed in 2012, with $370 million in new awards slated for review by the governing board and a new strategic plan that will help guide the agency's priorities going forward. The awards scheduled for review this year include the next round of Creativity Awards worth $2.2 million, which fund high school students to carry out research in California stem cell labs. Last year's students who participated in our pilot program were outstanding, as you can see in this video:

The governing board will also be considering research awards that cover the complete therapy development pipeline (you can read more about that development pipeline on our website). The fourth round of Basic Biology awards, worth up to a total of $35 million, will continue CIRM's commitment to funding the basic discoveries that fuel new therapy ideas and also help resolve scientific issues that arise further down the pipeline.

The Early Translational III awards, worth up to a total of $95 million, will fund researchers who are in the early stages of translating a basic discovery into a future therapy. Some of our past recipients of Early Translational Awards have had such success that they are now applying for our second round of Disease Team Awards, worth up to $240 million. As with the past round of these awards, the disease teams include people with clinical, research and regulatory expertise who work together to bring their therapy candidate to clinical trials.

If you don't already receive CIRM press releases or monthly newsletters you can sign up here. They'll include information about awards we've funded and other decisions by the governing board.

A.A.

Guest blogger Alan Trounson — December’s stem cell research highlights

2012-01-03T09:50:00.000-08:00

Each month CIRM President Alan Trounson gives his perspective on recently published papers he thinks will be valuable in moving the field of stem cell research forward. This month’s full report, along with an archive of past reports, is available on the CIRM website.

My review this month starts with a couple papers that further cement the high value of reprogrammed iPS cells as “disease-in-a-dish” models. This time they found the underlying mechanisms of the autism seen in Timothy Syndrome (blogged about here) and the bone and cartilage abnormalities seen in Marfan Syndrome.

But I want to take this space to note a different type of paper, one discussing a single patient, but a patient that would probably not be alive today without stem cells and a very creative international team of scientists. The team headed by a group at the Karolinska Institute in Sweden also had inputs from researchers in England, Germany and Iceland.

The patient had recurrent cancer in his trachea and little hope with traditional therapy, so the team built him a new airway. They first imaged his diseased trachea with a CT scan and then used that picture to build an artificial polymer scaffold of the same size and shape. They seeded this replica with stem cells from the patient’s own bone marrow and grew it in a bioreactor for 36 hours.

The new trachea was functional at the time of transplant, but the team gave the patient two growth factors to enhance the maturation of the airway. It seems like the patient’s own repair systems also kicked in because the team was able to detect other stem cells summoned to the site and other growth factors released by neighboring cells.

The patient is alive and cancer-free five months after the surgery. He is living “proof of concept” for an entire branch of regenerative medicine that seeks to build replacement tissues to order. We blogged about this advance here.

I began blogging about my science picks just a few months ago. You can read my 2011 science highlights in review in the following blog entries:

A.T.

The war on cancer: 40 years later

2011-12-23T10:37:00.000-08:00

Forty years ago today President Nixon signed the National Cancer Act, allocating $1.5 billion over three years for cancer research.

The Dana-Farber Cancer Institute has written an excellent piece on their blog about where the field has come since 1971. They write:

Forty years later, the War on Cancer can claim countless successes against one of the most resilient and recalcitrant enemies mankind has faced.

Some cancers that were once almost invariably fatal, such as pediatric leukemia, are now cured in the vast majority of cases. In kidney cancer, the five-year survival rate – the percentage of patients alive five years after diagnosis – has increased from about 50 percent in 1971 to more than 70 percent today. In colon cancer, the rate has increased from 52 to more than 66 percent over the same time period. Death rates for cancers of the breast, liver, lung, prostate, and several other organs and tissues have been declining for the past 10-20 years.

…

Despite all the strides over the past 40 years, cancer remains one of the biggest health challenges we face. The good news is that advances in the understanding of cancer at the basic, molecular level have positioned us to make even greater progress in the years ahead.

CIRM is playing an active role in the ongoing search for better cancer therapies. Of our disease-focused awards, cancer makes up 22% of our funding (you can see charts of our funding allocations here).

CIRM has eight awards working towards new therapies for cancers including leukemias and solid tumors such as those that form in the colon, brain and ovaries. Of those, four projects (two in leukemia and two in brain tumors) are part of our disease team programs, which all have the goal of submitting an application to the Food and Drug Administration by 2014 to begin a clinical trial. You can see a list of all our therapy development projects with links to those project descriptions in our online portfolio.

Although we can’t know in advance which of these projects will be successful, CIRM is proud to be part of the ongoing search for new cancer therapies.

A.A.

CIRM Spotlight on Heart Failure: A stem cell trial shows promise for healing injured hearts

2011-12-21T13:26:00.000-08:00

Todd Dubnicoff is CIRM’s videographer and video editor

At many CIRM governing board meeting, we set time aside to hear from researchers, clinicians, and patients about the hope of stem cell research in a particular disease area. We film each of these Spotlight on Disease seminars so that the scientists’ progress and the patients’ stories are available to the public (a video archive of past Spotlights is here). At the December 8th Spotlight, the board heard about the hope for a stem cell based heart failure treatment that is showing promising results here and now in a clinical trial for patients (watch that video here).

“An easy painless miracle.” That’s the way Fred Lesikar, one of the Spotlight speakers and a clinical trial participant, described the procedure that used his own heart stem cells to regenerate his scarred heart tissue injured by a massive attack two years ago at the age of 59.

The procedure is straight-forward: clinicians obtain a small tissue sample from the patient’s heart during a 15 minute procedure under local anesthetic. Under specific laboratory conditions, stem cells spontaneously grow out of this tissue sample. These cells are then harvested and delivered back into the patient’s coronary artery. Lesikar told the board that he is thrilled with the results:

I was in pretty bad shape…Next week it will be two years since I had the stem cells put in…it wasn’t like a light switch going off but by the time I got to a year I was feeling great…Now I’m flying down to Costa Rica tomorrow, the day after tomorrow I’ll be tromping through the jungle and my only concern is that the people with me aren’t going to be able to keep up.

Eduardo Marban, MD, PhD, director of the Cedars-Sinai Heart Institute, led this first-in-human clinical trial and was the main speaker at this month’s Spotlight. Marban summarized the hallmarks of heart failure after a heart attack and described the results of the trial:

One quarter of heart attack patients end up with so much scar that life expectancy is compromised…Once the scar occurs it’s irreversible…At one year, the subjects receiving the stem cell therapy have 12 to 13 grams less scar than they did at the beginning of the study. That in of itself is a good thing but what really got us excited was the fact that when we looked at the living heart muscle, those subjects have 22 grams of new living heart muscle…That's equivalent to restoring about half or more than half of the lost heart muscle in these subjects (compared to no change in control subjects).

Marban also showed results of pre-clinical studies funded by a CIRM Disease Team grant, which uses an alternate preparation and delivery method of the heart stem cells. These studies will form the basis of an FDA application in the second quarter of 2012 to perform a follow-on clinical trial.

T.D.

Stem cell science meets public health: Case study, Parkinson's disease

2011-12-20T09:01:00.000-08:00

Geoff Lomax is CIRM's Senior Officer to the Standards Working Group

As a student of public health, I havealways been a believer in public science. Public science is critical forproviding sustained capacity for research. As othershave pointed out, this capacity translates into important commercial potential.Historically, California has been a leader in investing in public science. Fromits network of universities and various health-oriented agencies, the statemaintains a wealth of information, technical and human resources. Capacity suchas this lays the groundwork for innovation as researchers from varyingdisciplines interact to imagine new ways forward.

One personally exciting conversationthat has emerged in the past couple of years is the role of stem cell sciencein supporting our understanding of environmental influences on health anddisease. In fact, the National Institutes for Environmental Health Sciences hasbegun to fundresearch addressing the potential of environmental exposures to alter function,proliferation, survival, and differentiation of stem cells (here is a link to that RFA). One area of particularinterest is the development of cellular systems to model the disease process.As we reported in a report on a toxicology meeting, these model systems help us both understand disease and evaluatetherapies.

At CIRM, we thought it would beinformative to hear from one of our grantee institutions that has beenexploring this space. At a recent seminar, researchers from The Parkinson’s Institute reported on their work studying the relationship betweenenvironmental influences and development of Parkinson’s disease. A novel studyin twins conducted by Samuel Goldman MD, MPH and Caroline M. Tanner, MD, PhD, fromThe Parkinson’s Institute has found that exposure to trichloroethylene (TCE) –a hazardous contaminant now found in soil, groundwater and air – can raise aperson’s risk of developing Parkinson’s disease by six times. That’s just oneof several contaminants and pesticides that increase risk of the disease.

The Parkinson’s Institute has takenskin samples from patients with the disease and reprogrammed those into anembryonic-like state. So far, they’ve developed 45 of these so-called inducedpluripotent stem cell lines (iPSCs). (Some of this work was done with a CIRM Early Translational Award.) In the process of developing these lines, researcherscollected information relating to environmental factors (job and residentialhistory, lifestyle and others) associated with health and disease. Dr. Birgitt Schuelediscussed ways in which these cells could be applied in future public healthresearch.

Oneintriguing line of inquiry related to examining how pesticide exposure may beassociated with Parkinson’s disease risk. Goldman and Tanner reported on howcertain pesticides cause Parkinson’s disease in animal models and exposure isalso associated with disease in humans. Schuele suggested patient iPSCs are avaluable tool for further studying this association and the disease process.The idea is that the researchers can mature those cells into the cell type thatis associated with the disease—called dopaminergic neurons. Then they canexpose those neurons to the pesticide to see if the neurons show signs of thedisease in a lab dish. This is a critical way of learning about the effects ofcompounds on human cell types.

Thistype of research represents a way to leverage existing investments inCalifornia’s unique information,technical and human resources. For example, the state’s pesticide use reportingand visionary investment in mappingtools offers a unique opportunity to connectbasic research on disease with information relating to the distribution ofenvironmental agents. Thanks to a bill supported by then-Senator Art Torres(now CIRM vice chair) California has the most comprehensive data on pesticide useof any state. These resources have been used previously to study other diseasesuch as autism. Videos from aseminar on the relationship between pesticide use and autism are available on CIRM’s YouTube channel.

The application of stem cell tools frombasic research towards public health and environmental protections represents acritical avenue for health promotion and disease prevention. It’s personallyexciting to see CIRM grantees making use of public resources to carry outscience with such a potential for public good, and to have the NIEHSrecognizing the value of this research with their funding initiative.

G.L.

Trounson predicts ripple effects from European court ruling on human embryonic stem cells

2011-12-16T08:56:00.000-08:00

In October the European Court of Justice issued a ruling that inventions created from human embryonic stem cells are not patentable. We wrote a few blogs at the time giving voice to different perspectives on what that ruling might mean. (Those blogs are here and here.)

This month, CIRM President Alan Trounson weighed in on the possible repercussions of the decision in the journal Cell Stem Cell (The abstract is available here, full access requires a subscription). Trounson’s letter is one of several opinions on the case that appear in this issue. Writing with Nancy Koch, CIRM legal Counsel, and Elona Baum, General Counsel and VP of business development, Trounson said:

Our view is that the impact of the recent Court ruling on stem cell research and regenerative medicine will be significant but varied. In some instances, the ruling may deter European hESC research, in others such research may nonetheless continue or even increase; in still others, no impact may occur.

The group wrote that they don’t expect the ruling to have a significant impact on basic research involving human embryonic stem cells. However, they suggest that the situation is more complicated for the type of research that translates basic human embryonic stem cell research discoveries into therapies. They write:

At this stage of research and development, profit-driven biotechnology and pharmaceutical companies are more actively involved. To the extent that the lack of patent protection following the Court ruling decreases the profit available (e.g., because patented inventions cannot be licensed and injunctions cannot be obtained to protect hESC patented inventions), biotechnology and pharmaceutical companies may be less motivated to invest in European hESC research. That effect may be even more dramatic for startup companies. A strong patent portfolio traditionally has been a prerequisite for attracting venture capital in the life sciences field.

However, they don’t predict a dearth of European commercial investment in embryonic stem cell research and technology. That’s because even though companies can’t patent discoveries, they may still be able to protect their work as traditional trade secrets. Moreover, the European regulatory authorities may require data from trials conducted in the EU before approving certain future stem cell-derived products

They also suggest that the ruling could lead to relocations both from the EU to the U.S. and the reverse. European companies whose business model relied on embryonic stem cell patents might relocate to the U.S. where those patents still hold. Companies in the U.S. who are slowed by patents held by others might relocate to the EU where those patents aren’t enforceable.

How these different factors play out remains to be seen, but the group does end on a hopeful note. They conclude by saying that they expect at least some of the critical human embryonic stem cell research taking place in the EU to flourish.

A.A.

Banking iPS and embryonic stem cells for easier access, consistent quality

2011-12-15T12:47:00.000-08:00

The board meeting last week was a day for following up on recommendations. In additional to the Opportunity Funds, which we blogged about earlier in the week, the board also approved a proposal for creating a stem cell bank. Stay with me here. This may not sound as exciting as funding new science or creating worldwide partnerships, but it’s important. Here’s why.

Imagine for a second that you decide you want to read those last few Jane Austens that you didn’t read in college. You go to the library, check them out, and enjoy. Right? But imagine that instead of going to a library you had to call around the neighborhood to track down the books, then drive to four different homes and sign four different book loan agreements and after all that some of the books have torn pages. It might seem like a better idea to just reread one of those old Agatha Christies on the shelf.

That’s where stem cell research is today. Say a researcher wants to compare stem cell lines from people with autism to find drugs that alleviate signs of the disease in a dish. That researcher would have to call around to several institutions, navigate a variety of materials transfer agreements and, basically, spend a lot of time on the phone rather than doing research. In yesterday’s blog, my colleague Geoff Lomax quoted Steve Peckman from the UCLA Broad Stem Cell Research Center talking about how these agreements –called MTAs—can hinder access to stem cell lines.

One way for CIRM to accelerate research is by creating more of a library system for stem cells – except we don’t want the cells back. This kind of bank is what was recommended at a banking workshop we held back in November 2010. (You can read a report from that workshop here.)

At last week’s meeting, Uta Grieshammer from our science office described CIRM’s $30 million proposal for creating such a bank. It will consist of three parts. First up will be awards to investigators who will go out and collect tissue samples from individuals with genetic diseases. The goal is to get samples from 1200 people.

Next, CIRM will give a single award to an organization that will take those samples and reprogram them into embryonic-like cells, called iPS cells. These cells have the ability to form every tissue in the body, and still retain the genetic make up of the person who donated the sample. These cells can then be matured into the cell type that goes awry in the disease as a way of studying that disease in a dish. In the past few years this technique has been used to create models of ALS, schizophrenia, Parkinson’s disease and autism, among others.

Finally, CIRM will fund a group to bank all these newly created cells, along with other stem cell lines. With this resource, that same researcher hoping to study autism cell lines could go to one place, navigate one materials transfer agreement and receive cells that are consistently quality controlled. The cells will be available to people in California and worldwide.

A.A.

Limited access to human embryonic stem cell lines? Survey says...

2011-12-14T11:00:00.000-08:00

Geoff Lomax is CIRM's Senior Officer to the Standards Working Group

Is the ability to obtain embryonic stem cell lines hindering research, what factors influence access, and does availability vary by state? These questions have been the subject research and their answers are not entirely clear. A recent publication in Nature by Aaron Levine of the Georgia Institute of Technology suggests that access issues do impact research. In his paper, he writes:

“an inability to acquire certain hESC lines have likely hindered hESC science in the United States.”

This conclusion is based on a survey of stem cell scientists in the United States. Levine focused his discussion on the subset who reported using human embryonic stem cells. A sizable number of these scientists--38%--reported excessive delay in obtaining lines and 28% reported they were unable to acquire a stem cell line they wanted to study. Factors attributed to delays included problems with materials transfer agreements (MTAs) and an inability to obtain approval from an institutional oversight committee. Based on these findings, Levine writes:

“These results suggest scientists in the United States cannot conduct comparative studies with a diverse set of hESC lines and suggest that access issues have contributed to this situation.”

I found these results intriguing because in a recent study quantifying the use of hESC lines by CIRM researchers, my colleagues and I found that scientists had obtained a diverse array of embryonic cell lines – 138 unique lines including 17 newly derived hESC lines. I suspected the apparent discrepancy in findings may be related to the research environment in California and other states with policies designed to support access to and creation of human embryonic stem cell lines. The answer to the question of whether availability varies by state is not clear because Levine’s responses are not geography correlated.

Our findings suggest widespread access in California, but it is important to keep in mind we examined what lines researchers ultimately accessed, not what they were unable to obtain. To gain further insight, I did a quick survey of my Science Office colleagues. Many hadn’t heard of cases where access to cell lines had been a deterrent to research for our grantees. I also queried grantees who were carrying out comparative studies. Jeanne Loring of the Scripps Research Institute has a CIRM grant to compare cell lines. When I emailed her she said:

“We've had no trouble getting hESC lines from collaborators all over the world. There are hundreds of cell lines available, and most are of good quality.”

Another colleague did recall instances where there were delays in obtaining cell lines, so I emailed Steve Peckman, who is Associate Director of the UCLA Broad Stem Cell Research Center. He did offer specific examples where material transfer agreements were a source of delay. In addition, Peckman indicated the NIH restrictions on the use of certain popular lines, such as HUES 9, did impact approval by institutional oversight committees even in cases where no NIH funding was involved, so perhaps California researchers were not immune to access issues.

Peckman also said that a game changer at UCLA was the ability to study newly derived UCLA 1-6 hESC lines created with CIRM funding (here is a list of all cell lines considered "acceptably derived" by CIRM). He suggested new cell line derivation has been a tremendous benefit for researchers, potentially attenuating problems encountered elsewhere. He noted, however, that UCLA and others are not well equipped to distribute lines outside their home institution, which could explain Levine’s findings that certain individual researchers were having a hard time accessing lines. Peckman’s solution was to support the development of a banking and distribution network with uniform material transfer agreements.

Peckman’s observations are reassuring in light of the decision by CIRM’s board to move forward with CIRM’s Human Pluripotent Stem Cell Initiative. The initiative includes a “Bank Award”. The concept proposal for this award says:

“California researchers have already generated many disease‐specific human induced pluripotent stem cell (hiPSC) and human embryonic stem cell (hESC) lines, many with CIRM funds… CIRM intends to provide funds for the establishment of an hPSC repository located in California that will bank and distribute high quality, disease specific hiPSC and hESC lines generated in California for research use.”

The comparative ease of access in California, as evidenced by Loring’s work, may be attributed to our comprehensive scientific, regulatory and facilities programs designed to facilitate research. CIRM’s programmatic efforts are consistent with Levine’s suggestion that “funding agencies … encourage research using multiple diverse hESC lines.”

We are always interested in hearing more. If you have experience accessing and utilizing hESC lines, we encourage you to comment below or contact me glomax@cirm.ca.gov.

G.L.

JDRF supports CIRM diabetes disease team led by ViaCyte

2011-12-13T13:54:00.000-08:00

Today a CIRM-funded disease team working toward a therapy for type 1 diabetes received additional support and endorsement from the Juvenile Diabetes Research Foundation (JDRF). The project, led by San Diego-based Viacyte, received almost $20 million in funding from CIRM in October 2009.

The goal of the ViaCyte project is to mature embryonic stem cells into a type of cell that normally produces insulin in the pancreas. These are the cells that are destroyed in people with diabetes. The group plans to put those cells in a device that protects them from the immune system, then implant that device in the body where it is hoped that the cells will mature to produce insulin in response to blood sugar. The cells are effective in animal models, the company says.

According to a press release from JDRF:

The three-year series of preclinical studies being co-funded by JDRF will help ViaCyte prepare the information necessary to apply for regulatory approvals to study the system for safety and efficacy in people with T1D.

The release goes on to quote leaders from JDRF, ViaCyte and CIRM:

"Encapsulation research is one of JDRF's priorities because of the profound possibilities it holds for many avenues of research for type 1 diabetes," said Julia Greenstein, JDRF's assistant vice president for Cure therapies. "We're excited about partnering with ViaCyte to explore the use of encapsulated stem cell-based replacement. This type of innovative therapy could revolutionize the way people live with type 1 diabetes, and may also reduce the risk of dangerous complications that often result from extreme high and low blood sugars."

"We are thrilled to be partnering with JDRF, the leader in the field of support for diabetes research," said Allan Robins, Ph.D., acting CEO from ViaCyte. "ViaCyte's goal is to create a product that will free people with diabetes from insulin dependence for the long-term, and we believe this therapy has the potential to transform lives."

"At CIRM, we have long had the goal of leveraging the financial and intellectual capital of California with other funds and talent from around the state and around the world, and the decision by JDRF is a clear example of how these partnerships can enhance the opportunities to get to the end goal of a therapy for patients," said Alan Trounson, president of CIRM. "We are proud to have JDRF as a partner in working with ViaCyte and their scientific team to bring a potentially life-changing therapy for people with diabetes to the clinic.

Here's more information about the ViaCyte disease team project and more about CIRM funding of diabetes research.

This video features ViaCyte's Eugene Brandon discussing the company's approach:

A.A.

Opportunity Fund addresses review panel's recommendations

2011-12-13T11:14:00.000-08:00

On December 8 of last year, CIRM received the insights and recommendations from a blue ribbon panel of external experts charged with evaluating the agency’s progress to date. (Here is a copy of that report, and CIRM’s press release.)

Less than a year later, on October 26, 2011 the ICOC approved the first of a three-part Opportunity Fund to address those recommendations. (A press release from October board meeting is available here.) And, just days ago on December 8th, a year to date from the expert’s report, the governing board approved the final two proposals. (That press release is available here.)

With all three programs of the Opportunity Fund approved, CIRM will be able to address the major recommendations of that panel: namely to create an agile and proactive grant program with flexible processes that synch up with industry, all geared at capturing great science and maintaining the progress of our strong research programs.

When CIRM first received the review panel’s report, the question was how could the agency address the recommendations within its legal and operational frameworks. All new science funded by CIRM has to go through a review by outside experts, which takes time, and state funds have to stay within California. To address these questions, CIRM held a brainstorming session to think about the most effective ways of meeting the recommendations.

What the CIRM science and legal offices came up with were three initiatives. The first of these, called the Strategic Partnership Funding Program, was approved at the October board meeting. This $30 million initiative responds to the review panel’s recommendation that CIRM attract industry partnerships through a funding approach that is more aligned with industry needs.

According to Elona Baum, CIRM General Counsel and Vice President of Business Development, who led the development of that program, the Strategic Partnership Funding Program will help our grantees team up with industry partners who can help them overcome regulatory issues and design effective clinical trials. These partners will also be needed to fund Phase III clinical trials.

The two pieces of the Opportunity Fund approved on December 8th are the $12 million Bridging fund, spearheaded by Patricia Olson, Executive Director of Scientific Activities, and the $15 million External Innovation Initiative, led by Ellen Feigal, Senior VP of Research and Development.

The External Innovation Initiative was developed as a way of leveraging California expertise to further great science taking place outside of California. CIRM has formed funding relationships with 12 countries, two international states, one domestic state, two foundations, and most recently CIRM’s collaborative relationship with the National Institutes of Health. (More information about those relationships is available here.) If great science is taking place in one of those jurisdictions, CIRM can facilitate a collaboration with a California scientist whose expertise will speed the science. CIRM only funds the portion of the research within California – protecting the state’s investment – but that funding can speed research toward disease therapies taking place around the world. Even if a therapy isn’t developed in California, Californians benefit from the results.

The Bridging Fund will play a critical role in keeping promising research moving forward. Imagine, you are a CIRM grantee with an Early Translational Award that produced promising results. But your funding ends, and you won’t know if you got your next CIRM award for several months. What do you do? You stop the research until you get more funding either from CIRM or from some other source. This stop and go nature of funding slows promising projects. The Bridging Fund will provide stopgap funding for those researchers who are waiting on the next big grant, keeping the research moving toward patients.

As Olson said, “I think these programs go a long way toward addressing the key concerns of the external advisory committee. Next comes implementation.”

The announcements describing each of these programs will be posted to the CIRM website in the first half of 2012.

A.A.

Jonathan Thomas reflects on the state of stem cell research

2011-12-09T12:42:00.001-08:00

Jonathan Thomas is Chair of the CIRM governing board

Yesterday our governing board met for the first time since Geron announced the decision to terminate their stem cell research program. I wanted to take that opportunity to address the board and let them know my strong commitment to CIRM’s stem cell research program.

When Geron made their announcement our immediate concern was for the patients and their families who were disappointed at the termination of a trial that was a source of such hope for the future. Geron has been a true leader in the field and a source of inspiration for patients and their families. They broke new ground, becoming the first to start a Food and Drug Administration-reviewed trial based on human embryonic stem cells. Their efforts laid the groundwork for the two additional trials now underway for forms of blindness and for those trials that are close to submitting applications to the FDA.

However, Geron is a business. The company decided that their cancer therapies were farther along than the stem cell trial and when they held the stem cell program against the prism of economic reality they made a business decision to end the trial. The company is now looking for a partner to carry the research forward.

There are those who have extrapolated Geron’s business decision to question stem cell science. I say to those people: If you were to query the many researchers worldwide and companies involved in developing products you would hear unwavering enthusiasm for pursuing stem cell technology.

I was just at the excellent Stem Cells on the Mesa meeting in La Jolla where I heard from those researchers and investors. We spent the first day hearing about the incredible scientific advances taking place in the stem cell field. The next day we attended a business and investor partnering forum (sponsored in part by CIRM) where the same message of enthusiasm for stem cell science echoed just as strongly.

CIRM’s award to Geron was just one of the 44 projects in 26 disease areas that are in various stages of working toward clinical trials. (I blogged about those projects recently.) We remain optimistic about those research programs and are totally committed to the projects we have funded to-date and to the research we will fund in the future.

J.T.

Stem cell discovery could help people regain smell

2011-12-08T11:25:00.001-08:00

Elongated green cells are sensory neurons – which sense smells andrelay that information to the brain – that originated from olfactorystem cells in the nose. Cells labeled in red are immature cells in theprocess of differentiating into neurons and other mature cell types.(Photomicrograph by Russell Fletcher, UC Berkeley)

A rose may smell as sweet by any name, but for those without a sense ofsmell a rose by any name still smells like cardboard. Now there's aglimmer of hope for those whose fine wine and roses are odorless andwho can't taste. Researchers at the University of California, Berkeleyhave found a gene that's responsible for prodding stem cells in thenose to form new odor-sensing neurons.

A press release by Robert Sanders at the UC Berkeley quotes leadresearcher John Ngai talking about the loss of smell in old age:

“Anosmia ‑ the absence of smell ‑ is avastly underappreciated public health problem in our aging population.Many people lose the will to eat, which can lead to malnutrition,because the ability to taste depends on our sense of smell, which oftendeclines with age.”

“One reason may be that as a person ages, the olfactory stem cells ageand are less able to replace mature cells, or maybe they are justdepleted,” he said. “So, if we had a way to promote active stem cellself-renewal, we might be better able to replace these lost cells andmaintain sensory function.”

The release goes on to quote Gary K. Beauchamp, director of the MonellChemical Senses Center in Philadelphia, who was not a member of theresearch team. He noted that the olfactory system stands out for itsability to regenerate following injury or certain diseases.

“This new paper … presents an elegantanalysis of some of the underlying genetic mechanisms regulating thisregeneration,” Beauchamp said. “It also provides important insightsthat should eventually allow clinicians to enhance regeneration, induceit in cases where, for currently unknown reasons, olfactory lossappears permanent, or even prevent functional loss as a person ages.”

The group found a gene that seemed to be involved regulating nasal stemcells. They created mice that lacked that gene and found that the micehad more than the usual number of odor-sensing cells. Sanders goes on towrite about how regulating this gene -- called p63 -- could helppeople regain a sense of smell:

A drug that regulates p63, or modulatesone of the genes that p63, in turn, regulates, might be able to boostthe number of nasal stem cells as well as the number that mature intosmell neurons.

Any real world result of this work would be many years off -- the pathfrom a mouse lacking a gene to a drug that's available to humans is along and arduous one.

Neuron, December 8, 2011
CIRM Funding: Russell B. Fletcher, Melanie Prasol (T1-00007)

A.A.

Mess with the body's clock, mess with stem cells

2011-12-06T13:08:00.001-08:00

The Canadian Stem Cell Network posted an interesting item on their blog today about the relationship between stem cells and our sleep/wake cycle (also called the circadian rhythm).

David Kent, a postdoctoral researcher at the University of Cambridge, writes about the work, which was published online in Nature November 9:

The group of Salvador Aznar Benitah in Barcelona recently published research which links skin stem cell turnover and heterogeneity to the body’s internal clock. Their work has inspired many new studies that aim to understand the impacts of circadian rhythm on other stem cell systems.

The group found that when they disrupt genes that control the sleep wake cycle, they also disrupted the balance of stem cells in a dormant versus dividing state in the mouse hair follicles. The blog goes on:

This disturbance in rhythm led to premature aging as well as an increased incidence of tumours, suggesting that we might better understand how cancers grow and progress by understanding the natural cycles our bodies go through.

In the Nature paper, the authors write:

Our results indicate that the circadian clock fine-tunes the temporal behaviour of epidermal stem cells, and that its perturbation affects homeostasis and the predisposition to tumorigenesis.

Translated, what the researchers are saying is that the body's daily rhythms helps control the behavior of stem cells, at least the ones in the hair follicles. Mess with the body's clock and you mess with the ability of those stem cells to carry out their normal functions, including regulating aging and tumors.

A.A.

Clocks & stem cells: Time and tinkering to develop the best embryonic stem cells

2011-12-05T08:14:00.001-08:00

Geoff Lomax is CIRM's Senior Officer to the Standards Working Group

The history of technology tells us that the first strategy is rarely the one that sticks. One of my favorite examples involves the English clock maker John Harris, whose many iterations of marine chronometers revolutionized sea travel. (His story is recounted in Dava Sobel’s excellent book Longitude: The True Story of a Lone Genius Who Solved the Greatest Scientific Problem of His Time.) My English grandfather also worked on clocks and marine guidance systems so I have a soft spot for the guild.

In 1730, Harris sought to produce a clock, called the H1, which could maintain accurate time on a lengthy, rough sea voyage with widely varying conditions of temperature, pressure and humidity – a great challenge in his day. This initial prototype performed well but there was a desire for a more rugged and compact design. After several iterations and another 23 years, he produced the H4, which kept time within 39 seconds during a trans Atlantic sea trial. A subsequent design, H5, was accurate within one-third of a second – revolutionary for its time.

Fast forward to 2011, in the world of human embryonic stem cell research, the cell line H9 has been revolutionary for its time – used in thousand of published studies. In a recent article, Rohun Patel and I illustrate how it is also the most widely utilized human embryonic stem cell (hESC) line by CIRM researchers. However, we also found that CIRM grantees were carrying out research with 137 other lines including 17 that had been recently derived with CIRM funding.

A recent study in Human Molecular Genetics authored by Amander Clark at University of California, Los Angeles suggests the newly derived CIRM lines may have several improvements over the earlier models. The study compared the X chromosomes of older lines, including H9, to recently derived lines. The UCLA team found that the X chromosomes in the newer lines were more active than those in the older lines, which tended to have more of the X chromosome shut down. Furthermore, the way in which those older lines shut down portions of the X chromosome deviated from how cells normally de-activate portions of the X chromosome – called “X inactivation”. In a press release from UCLA Clark said:

“The classic signature is gone, so something else is regulating X chromosome inactivation in the established cell lines,” Clark said. “It will be important not only to find out what that is, but also to discover what else is changing in the nucleus that we cannot see.”

Clark’s paper shows that in stem cell research—as in other areas of innovation—it takes time and tinkering to develop the best model. The ability of CIRM-funded researchers to develop and then investigate 17 new human embryonic stem cell lines and access hundreds of others would not be possible under federal guidelines alone. Federal agencies like the NIH can’t fund research to create new stem cell lines. Clark’s paper shows the clear need for these efforts to continue under CIRM and other agencies that fund cell line derivation. In the press release she said:

“Our data highlights the importance of maintaining hESC derivation efforts. Gold standard hESC lines should be the benchmark for human pluripotent stem cell research.”

Unlike Harris, stem cell researchers don’t have 23 years to tinker with their design. Patients need therapies soon, and therapy development will be bolstered by having optimal tools available to all researchers. Clark’s work shows the value to patients in those 17 lines derived by CIRM grantees, and by all those other new lines that have been and will continue to be created through sources other than federal funding.

Human Molecular Genetics, November 30, 2011
CIRM Funding: Amander Clark (RL1-00636-1)

G.L.

Guest blogger Alan Trounson — November’s stem cell research highlights

2011-12-02T11:07:00.001-08:00

Each month CIRM President Alan Trounson gives his perspective on recently published papers he thinks will be valuable in moving the field of stem cell research forward. This month’s report, along with an archive of past reports, is available on the CIRM website.

This month’s literature produced a number of studies that can be glibly summarized as: Hey they work; they really work. The publications show we are starting to get a real handle on how to get stem cells to integrate and function like the desired tissue, and even to form complex structures.

The same Japanese team that was able to create a complex optic cup in a dish earlier this year, now reports that they have used embryonic stem cells to create a pituitary gland. That gland secretes the appropriate hormones and is able to correct hormone deficiency when transplanted into a mouse that lacks the pituitary gland, making the formerly lethargic animals active again.

Two teams turned embryonic stem cells into neurons that were able to integrate into the brain and show evidence that they function like the specific type of neuron that each team sought. A New York team produced dopamine-producing neurons that were able to correct some movement disorders in Parkinson’s disease models in mice, rats, and monkeys. (We blogged about that work here.) Meanwhile a Wisconsin team chose to mature the stem cells into neurons designed for memory, those in the hippocampus, and showed that they were able to integrate and fire neural signals like neighboring cells.

A Carolina team used a type of stem cell found in bone marrow and fat, mesenchymal cells, taken from the father of sheep with hemophilia, and correct the hemophilia in their sons. They did it by harvesting the stem cells and then genetically altering them so they produced Factor VIII, the blood-clotting factor that hemophiliacs don’t produce. When given to the sons, their bleeds stopped including the bleeds into their joints that had made them limp badly. The animals were able to walk normally again after the injections.

I start this month’s report with a pair of papers that seem to sort out some of the conflicting data that has been reported on stem cells for heart repair. One showed that stem cells from the bone marrow given in a couple of weeks after injury do not do improve heart function. Another showed that a different cell type—cardiac stem cells harvested from the patient’s heart—given even months after evidence of heart failure, were able to improve heart function, and in some patients for at least a year. (We blogged about that work here.) This is a critical area to gain some clarity in what cells to use and when; the burden of heart failure is a huge drain on our nation and the world.

My full report of this month’s highlights is here. I hope you will find it interesting.

A.T.

World AIDS Day 2011 -- Buzz about a Cure for HIV, CIRM Leading

2011-12-01T12:14:00.001-08:00

Jeff Sheehy is director for communications at the AIDS Research Institute at UCSF, and a member of the CIRM governing board.

Two articles in major newspapers—the New York Times and London's Financial Times—are highlighting the growing movement advocating for research towards a cure for HIV in the lead up to World AIDS Day on December 1.

Advocacy for a cure has been sparked in recent years by the experience of Timothy Ray Brown, the first patient cured of HIV. It has been five years since his dangerous and high-risk procedure that also cured his leukemia and his virus remains undetectable. More recently, a patient who had some of his disease fighting T-cells re-engineered with a HIV-resistant gene is showing preliminary signs of having virus suppression without antiretroviral medications for a significant period of time. (We blogged about that work here.)

Despite these successes let's be clear, a cure is still many years off and will require the active participation of patients motivated by altruism—as my friend Nelson Vergel has noted, heroes for the cure are needed. As Vegel writes, “No one really knows the degree of altruism in the community and their willingness to accept risks for the good of all.”

But recent data from UNAIDS shows us that those heroes for the cure and the cures themselves are desperately needed. While the number of new HIV infections has stabilized and the number of deaths due to AIDS is decreasing, we are seeing two new infections for every one person we manage to get into treatment globally. We are still losing ground against the epidemic.

And in the U.S., the federal Centers for Disease Control announced this week that only about a quarter of the 1.1 million people in the U.S. living with HIV have been successfully treated with antiretrovirals to a point to where they have suppressed the virus in their bodies to very low levels.
A cure is the best way to permanently change these statistics.

The California Institute for Regenerative Medicine, of which I am a board member representing HIV/AIDS, has provided historic leadership in funding future cures. The first applications were accepted for blood and immune system stem cell (hematopoietic stem cells) gene therapy projects to permanently re-engineer a person's immune system to resist HIV almost 4 years ago. Two awards were approved two years ago (one to City of Hope and one to UCLA) and should be in clinical trials within another 2-3 years. The challenge of replicating Timothy's daring proof of concept experiment in a much safer and much more scalable manner was taken up by CIRM while the head of NIH's HIV/AIDS programs was pooh-poohing the approach as ''not practicable." He has now embraced the call for a cure and it has become one of his top research priorities.

When California voters approved Proposition 71 seven years ago, none of us knew where the science might lead. And one cannot promise a specific cure for HIV or any other disease. However, I know that the existence of CIRM has greatly helped to change the research agenda for HIV globally and I suspect this is true for many other diseases and conditions.

CIRM, the California stem cell institute, does not propose temporary or episodic relief from disease, pain and suffering. We are committed to finding cures and we are working towards them relentlessly in partnership with patients, researchers and industry across California. This year on World AIDS Day, 30 long years into the HIV/AIDS epidemic, CIRM is a beacon of hope.

This video features Jeff Sheehy and CIRM disease team leader talking about a CIRM-funded project for HIV/AIDS:

J.S.

CIRM helping stem cell scientists and investors pair up

2011-12-01T08:30:00.001-08:00

In La Jolla, stem cell scientists, companies and investors are engaging in a series of CIRM-sponsored get-to-know-you meetings as part of the first ever partnering forum in conjunction with the annual Stem Cell Meeting on the Mesa. These meetings are part of CIRM's ramped-up efforts to help scientists overcome obstacles on the path to clinical trials.

Elona Baum, CIRM General Counsel and Vice President of Business Development, was one of the primary organizers of the Investor and Partnering Forum. She said:

"The forum will feature company presentations and industry discussion panels on regulatory, finance, commercialization and reimbursement issues. The Forum will provide the opportunity for hundreds of business, academic research and investor participants to connect for one-on-one meetings and strategic partnering."

CIRM has 43 projects in various stages of working toward clinical trials (more information about those projects is available here). Getting from their current status through clinical trials will require significant investment. It takes big money to gather the kind of preclinical data the Food and Drug Administration (FDA) needs to see before allowing a product to enter first-in-human clinical trials. CIRM funds preclinical through early phase clinical trials, but researchers in academia also need to seek funding from other sources to gather sufficient data, and engage industry partners early to help carry their work into the clinic and the subsequent development steps towards regulatory approval.

Forming the partnerships that will allow academic researchers and researchers at young biotech firms to see their work eventually reach clinical trials is what the La Jolla meetings are all about. It's a chance for stem cell researchers to pitch their work to investors in the hopes of finding a good fit. They can also attend a series of sessions about how to navigate the regulatory pathway and form collaborations, among other sessions.

This forum is one of several ways CIRM is trying to help academic scientists succeed in getting their research translated into therapies. CIRM continues to hold conversations, roundtables and webinars with the FDA, the agency regulating investigational products and whether and when they can enter clinical trials. By having conversations now, CIRM can help researchers meet FDA requirements enabling them to enter their products into clinical trials. CIRM’s webinars to inform its grantees about different areas of stem cell research and the regulatory path are also publicly available to view on the CIRM website.

A.A.

Autism-like syndrome modeled by in a lab dish

2011-11-30T12:51:00.001-08:00

One of the biggest hurdles in understanding and treating neurological diseases is figuring out what has gone awry with those cells. People aren't generally eager to donate a chunk of their brains for research. With the advent of reprogrammed iPS cells scientists have been able to recreate the diseases in a lab dish and begin to understand the origin of those diseases.

In the past few years, CIRM grantees have taken skin cells from people with Parkinson's disease, schizophrenia and forms of autism, reprogrammed those into embryonic-like cells, and matured them into the cells that go awry in the disease. (We blogged about Parkinson's here, schizophrenia here, and one form of autism here.)

The latest of these studies comes from CIRM grantee Ricardo Dolmetsch at Stanford University, who has created nerve cells out of people with the rare genetic disorder called Timothy Syndrome that includes autism as a symptom. Dolmetsch came to this research for personal reasons. In a conversation with Paul Costello in Stanford's 1:2:1 podcost, he talked about his son, who was diagnosed with autism at age 4. In that interview he told Costello how that diagnosis altered the direction of his work:

"The thing that was disconcerting is that I'm an academic and I was horrified to discover that very little was known. And so I thought I'm a neurobiologist and I don't work on this but at least in principle I could. And so I decided to turn my lab toward studying autism."

As a part of that new research direction, Dolmetsch got a CIRM Tools & Technologies II award to use nerve cells created from the skin of people with Timothy syndrome to attempt to find drugs that reverse the symptoms, at least in the lab dish. A Stanford press release describes their findings:

In this study, the scientists suggest that the autism in Timothy syndrome patients is caused by a gene mutation that makes calcium channels in neuron membranes defective, interfering with how those neurons communicate and develop. The flow of calcium into neurons enables them to fire, and the way that the calcium flow is regulated is a pivotal factor in how our brains function.

The researchers also found brain cells grown from individuals with Timothy syndrome resulted in fewer of the kind of cells that connect both halves of the brain, as well as an overproduction of two of the brain’s chemical messengers, dopamine and norepinephrine. Furthermore, they found they could reverse these effects by chemically blocking the faulty channels.

In the release, Dolmetsch points out that although they did fund a chemical that reverses the effects, that chemical, called roscovitine, is not currently approved for use in humans and has never been tested in children. He said:

“The reported side effects are probably due to the fact that, in addition to targeting the channel that is mutated in autism, roscovitine also inhibits kinases that are required for cell proliferation. We think that roscovitine is a good starting point, but probably has to be optimized before it would be useful for autism.”

Nature Medicine, November 27, 2011
CIRM funding: Oleksandr Shcheglovitov (T1-00001)

A.A.

San Diego area gets stem cell "Collaboratory"

2011-11-29T10:49:00.001-08:00

Sanford Consortium for Regenerative Medicine

Today the ninth of twelve CIRM-supported stem cell facilities in California is opening its doors. The Sanford Consortium for Regenerative Medicine in La Jolla will be home to stem cell scientists from five San Diego area research centers — University of California San Diego, The Salk Institute, The Scripps Research Institute, The Sanford-Burnham Medical Research Institute and the La Jolla Institute for Allergy & Immunology.

As with all of the CIRM-supported facilities, the institute's support leveraged public and private funds to build a facility that provided construction jobs and that will drive the local biotechnology industry, in addition to being a center for developing new therapies. CIRM provided $43 million to support the $127 million facility. Another $19 million came from philanthropist T. Denny Sanford, with the remainder coming from public and private sources.

According to a story in the North County Times:

That construction put money into the pockets of local builders, architects and other professionals. But the real economic benefit is to come from the research the building is expected to engender, and the products local companies hope to take to market.

The story goes on to quote Louis Coffman, consortium vice-president, talking about the way the building was designed to promote collaboration:

"In terms of collaboration, we believe that you cannot force it," Coffman said. "You can't make it happen. It's sort of an emergent property of people working together. They either work together or they don't. All we can do is create the conditions to enable it to happen."

A story in the San Diego Union Tribune discusses the collaborative nature of the building and quotes CIRM President Alan Trounson discussing the value of encouraging scientists to work together:

The new building has been nickhamed the “Collaboratory” for its emphasis on teamwork. The center’s interior features almost 3,000 square feet of glass so that scientists from different disciplines will regularly see one another. Laboratories are linked by informal meeting areas. And seating in the auditorium was limited to 150 in the belief that crowds bigger than that discourage people from being social.

“The design means that you can’t walk from spot A to B to C without meeting other people,” said Alan Trounson, president of the California Institute for Regenerative Medicine (CIRM), a state agency that provided $43 million in public funds for the project. “This is not a conventional building. The idea is to integrate people from various places. Instead of taking a year and a half to meet, they’ll have done so in three months.”

That Union Tribune story includes some highlights about the scientists who will be housed in the new facility and some of the technologies San Diego stem cell scientists will have access to.

The opening of the Sanford Consortium building also kicks off the annual Stem Cell Meeting on the Mesa, which includes a first-time partnering forum to bring together the investors, companies and academics who will need to work together to bring stem cell therapies to patients. We'll have more on that forum in future blogs.

Last month the UC Berkeley stem cell facility opened, which you can read about here.

-A.A.

Jonathan Thomas on CIRM's progress toward stem cell therapies

2011-11-23T09:58:00.001-08:00

Jonathan Thomas is Chair of the CIRM Governing Board

When I became Chair of CIRM this summer one of my first priorities was to reach out to the people of California and explain the progress we’ve made in developing new therapies. The agency only started funding research in 2007 and yet we already have 43 research projects that are in various stages of progress toward clinical trials.

At my first board meeting as chair, I and the rest of the board were excited about a presentation by Ellen Feigal, senior VP for R&D, and Pat Olson, executive director of scientific activities. They gave a detailed summary of all CIRM’s projects that have a goal of developing a therapy for one of 26 different diseases. Their summary, though exciting, was pretty technical. I thought if only the information were written in clear easy to understand language for the people of California, they couldn’t help but be as excited as I am about the agency and what it has accomplished. (We blogged about that presentation here.)

That summary is now available on our website, including a list of our awards that are in stages of developing therapies for 26 different diseases. We also explain the process our grantees go through to turn a basic science discovery into a new therapy, and we have information about what CIRM is doing to help smooth that pathway to get therapies to patients faster.

CIRM progress toward therapies

(You can also download this information in a PDF document.)

Given that it normally takes a decade or longer for a basic science discovery to reach clinical trials, 43 projects seemed to me like quite an achievement – an achievement that the people of California should take pride in supporting. Not only is CIRM driving stem cell science in our state, but through our national and international collaborations California has become a stem cell hub that accelerates stem cell progress worldwide.

I hope everyone who reads about our projects is as hopeful as I am about the future of stem cell therapies. As my friend Roman Reed says, CIRM is turning stem cells into cures.

J.T.

Hope for treating heart disease with stem cells?

2011-11-17T14:15:00.001-08:00

It's a big day for announcing prizes to CIRM grantee, and a good week for stem cells in heart disease. CIRM scholar Li Qian from The Gladstone Institutes won the Louis N. and Arnold M. Katz Basic Science Research Prize for Young Investigators from the American Heart Association (AHA). Hers was one of several announcements this week regarding the potential treatments for heart damage after heart attack.

According to a press release from The Gladstone Institutes:

"Dr. Qian received the prize for her findings that non-muscle cells that normally form the architectural support for the heart can be reprogrammed into beating heart muscle cells. This reprogramming may allow scientists to transform non-beating scar tissue resulting from heart disease—and which was previously considered irreparable—into beating tissue again."

Qian is carrying out her work in the lab of CIRM grantee Deepak Srivastava, who last year published work in which he and his colleagues converted mouse heart support cells called fibroblasts into beating heart cells in a laboratory dish (read our blog about that work here). For Qian's work, which was presented at the AHA meeting in Orlando, she and Srivastava carried out the same feat in a living mouse. The team delivered factors directly into the hearts of mice with induced heart attacks (you can read the abstract for that work here). Those injections seemed to have induced support cells to convert into heart muscle cells, and three months later the mice had less heart dysfunction than their labmates who hadn't received the injections.

Of course, mice aren't humans and three months isn't long enough to know if the benefits of the injections will last.

This award comes during what has been a big week for stem cells in heart disease. For many years now, research groups have been testing stem cells isolated from the bone marrow to see if they can effectively treat damage from heart attacks. Results had been ambiguous. Researchers saw some improvement, but it seemed to be short-lived in most studies.

In studies published earlier this week, a group from Louisville and a group of CIRM grantees from Cedars-Sinai both published results suggesting that stem cells isolated from the heart could produce improvements that last up to a year.

ABC News spoke to one of the patients who participated in the University of Louisville trial:

Mike Jones, the very first patient to receive the treatment in July 2009, said it not only gave him more years to live, but a better quality of life during those years.

"Now I can do more with my grandkids," said Jones, 68, who lives in Louisville. "I pitched softballs with my granddaughter for probably 15 minutes today. I got a little bit winded at the end, but that's something that before the stem cells would have been just impossible."

These studies involved small numbers of people and the results need to be confirmed in much larger trials. Still, those of us with heart disease in the family will be watching to see how the cells fare in the larger trials. My own grandfather, unlike Jones, would not have been able to pitch softballs after his heart attack.

A.A.

Presidential Award goes to UCSF high school internship program hosting CIRM-supported students

2011-11-17T07:14:00.000-08:00

Last summer CIRM sponsored high school students to carry out stem cell research at five California universities in association with existing high school internship programs at those schools. Yesterday we learned that President Obama likes our choice of partner programs — the UCSF program that included six CIRM-supported students received the Presidential Award for Excellence in Science, Mathematics, and Engineering Mentoring. That award to the Science & Health Education Partnership (SEP) High School Internship Program comes with a $25,000 grant.

The SEP program is focused on drawing students from disadvantaged backgrounds and giving them experiences that will help them succeed in college. In a press release, UCSF described their students:

The program works closely with San Francisco high school science teachers to identify students from disadvantaged backgrounds with significant potential. For example, the majority of high school interns come from families where neither parent has completed college. The education outcomes of students who participate in the internship program far exceed that of their peers - 92 percent matriculate to college, 76 percent complete Bachelor's degrees in the sciences, and 87 percent pursue post-baccalaureate degrees.

Congratulations to the UCSF team, and to the outstanding students who have gone through the program.

CIRM science officer Mani Vessal led the high school internship program for CIRM. The awards—called Creativity Awards—encourage participants to carry out research in an additional field unrelated to stem cell research. He said:

It really does foster creativity to have a mulitlinear approach to learning as opposed to just a single dimensional one. We're hoping to get the next generation of stem cell scientists who can think outside the box.

This short video features Ben Koo, the Academic Coordinator for the SEP program, and Creativity Award students from the UCSF and other programs talking about their research projects.
:

After last summer's success, CIRM is expanding our Creativity Awards program for next summer. The request for applications just got posted to our website.

A.A.

The First International Vatican Adult Stem Cell Conference: A Gound-Breaking Achievement

2011-11-16T13:27:00.000-08:00

John Wagner is Professor and Director of the Division of Pediatric Blood and Marrow Transplantation at the University of Minnesota Medical School. He performed the first umbilical cord blood transplant to treat a child with leukemia and pioneered the use of stem cells in the treatment of the skin disease epidermolysis bullosa. He is also a member of CIRM’s standards and grants working groups.

It was a fascinating week in Rome where I was one of several invited speakers attending the Vatican sponsored: “Adult Stem Cells: Science and the Future of Man and Culture.”

Overall, I was personally ‘moved’ by the uniqueness of this event that mixed science and history. Regardless of anyone’s personal religious beliefs, the Catholic Church does have an undeniable place in the history of western civilization with a legitimate obligation at least for Catholics and Catholic institutions around the world to try to understand the broader impact of science that no longer simply observes nature but now has the capacity to alter it.

My specific role was to highlight some of the ‘lessons learned’ from ‘our’ collective experiences with blood-forming stem cells, the only stem cell therapeutic with proven regenerative medicine potential. Those lessons learned include best practices in ethical conduct in high-risk clinical experimentation in vulnerable populations, the obstacle of the immune response and the need for earlier considerations on issues of access to new technologies and public education on reasonable expectations for phase I studies.

In addition to my contribution, there were a host of other presentations focusing on public confusion on what stem cells are and the public’s understanding of the regenerative capacity of embryonic versus adult stem cells, the impact of politics particularly in the United States, sources and types of adult stem cells, technological advancements in organ and tissue regeneration, regulatory requirements for stem cell therapeutic manufacture from industry’s perspective, and clinical applications in neurological, cardiovascular, autoimmune diseases. These talks were intermixed with moving testimonials from patients who are looking to stem cells as a source of future therapies. Intriguingly, the Conference was also about ‘building bridges’ between the Church and scientists to enhance bioethical-humanistic-cultural considerations of stem cell research and develop strategies for educating the present and future generations of students in the life sciences.

As would be expected, the meeting had a strong focus on the promise of adult stem cells with relative silence on the impact of embryonic stem cells. Statements by others on the ethics of stem cell research were also predictable—“the destruction of the human embryo is never justifiable regardless of any claim to therapeutic benefit“(although it was often stated that any benefit from embryonic stem cells has yet to be demonstrated).

But, there were indeed surprises as well: 1) the Church voiced its desire to open a dialogue with scientists and educators in the life sciences, and 2) the Church announced its unprecedented financial investment into promoting adult stem cells and their role in regenerative medicine.

While we might have wished for more detail on how the Church planned to build such bridges and open dialogue with scientists, the intent was seemingly sincere. In fact the Church had already identified ‘partners’ whose work would itself promote adult stem cell research including neural stem cells derived from recently aborted fetuses, which are already in clinical trials for several conditions. The Church also clarified that its financial investments were principally focused on public education, such as through the Stem For Life Foundation, the philanthropic arm of NeoStem, Inc. which co-sponsored the Conference.

Despite the fact that my views might differ from those of some of the presenters, I was amazed by the uniqueness of this event that placed the science of today into an historical context. Consider the venue and the associated events that included a dinner reception at the Casina Pio IV (the Vatican Academy of Science), a concert at the Basilica of St John Lateran, and an audience with Pope Benedict XVI. At the end of the day, I had the feeling that perhaps this self-proclaimed ‘ground breaking’ achievement was more than self-aggrandizement. Perhaps, the Church indeed strived to promote dialogue and build bridges with those deeply involved in the science of stem cells and its clinical translation into meaningful therapeutics. For sure, the moral status of the embryo may be front and center in terms of the ethical issues, but there are other issues as well that need further discussion regardless of the stem cell source. The creation of such a dialogue on the broader philosophical and humanistic aspects of science in general and stem cell research in particular must be a good thing.

If we agree that the goal of science is the discovery of new knowledge and truth—and en-light-enment—we must also acknowledge that there are risks, such as those realized with the nuclear experiments of the last century. And, recall in Mary Shelley’s Frankenstein: A Modern Prometheus, that the not too distant cousin of light is fire. So, perhaps, it is not unreasonable to listen openly and dialogue with others who may have opposing but reasoned views, with the understanding that you need not completely accept all that others speak. From there new knowledge and a higher level of discourse may take place. If successful, that, in and of itself, would be a ‘ground breaking’ achievement.

John Wagner

Q&A about Geron's decision and its implications for the stem cell field

2011-11-15T15:24:00.000-08:00

Yesterday Geron announced that they would be discontinuing their embryonic stem cell program, including the groundbreaking spinal cord injury trial that CIRM had been supporting. You can read more about the decision in Geron's announcement and in CIRM's press release. Geron has returned the $6.4 million they had received from CIRM with accrued interest.

It's not uncommon for companies to discontinue research programs for financial reasons. What makes this announcement different is the high-profile nature of the company and the trial. Geron was the first to pave a path through the Food and Drug Administration (FDA) to test a human embryonic stem cell-derived product in clinical trials. The trial was seen as a sign of hope for people waiting for therapies derived from embryonic stem cells, so its termination came as a shock to many patients and their families.

Today we wanted to take a step back and look at the announcement and what it means.

Q. What was Geron testing in their spinal cord injury trial?
A. Geron started with human embryonic stem cells and matured them into the precursor of type of cell that forms the coating on neurons. That coating is lost soon after a spinal cord injury, and without the coating electrical signals can't travel up and down the spine. The idea was that after injecting some of these precursor cells they would mature and form a new coating on the spinal cord neurons, restoring the ability of signals to cross the injury site.

This first trial was in its early stages and was testing a low dose of the cells to make sure they are safe. Remember that when this trial began the cells had only been tested in animals. Only after the company showed that the cells were safe would they be able to inject a dose that was expected to be high enough to show some signs of success.

Q. Why did Geron decide to discontinue the stem cell program?
A. The company decided to focus its resources on two oncology drugs that are in clinical trials. The decision was made based on financial considerations, not based on concerns about the science. Such a move is relatively common for biotechnology companies especially during the complex early-phase clinical trials such as this one.

Q. What does Geron’s decision mean for the field of stem cell research?
A. The field of stem cell research continues to be strong, with many promising therapies in the pipeline. Geron leaving the field does not alter the existing excellent programs that are working toward and carrying out clinical trials.

Q. What will happen to the patients who already received the cells?
A. Geron has been closely following the patients who have received the cells. So far, the patients have tolerated their injections and haven't shown any serious adverse effects from the cells. The company says it will continue monitoring those patients and keeping the FDA appraised of the results.

Q. Will the trial continue?
A. For now, the trial is discontinued. Geron says they are looking for partners to further develop their stem cell programs. Whether or not the trial continues depends on whether partners come forward with the resources and the interest in continuing it.

Q. What happened to CIRM's money?
A. CIRM had committed $24.8 million to support the trial, of which $6.4 had been dispersed. Geron has already returned the money in its entirety with accrued interest.

Q. Are there other trials testing products made from embryonic stem cells?
A. Yes. The company Advanced Cell Technology is testing an embryonic stem cell-derived product in two forms of blindness: macular degeneration and Stargardt's disease. They have already begun enrolling patients in those trials.

Q. What other trials are in the pipeline to test embryonic stem cells?
A. World-wide, many groups are moving closer to clinical trials testing cells derived from embryonic stem cells. CIRM has funded four disease teams that have the goal of submitting a request to the FDA to move forward with clinical trials (that request is also known as an Investigational New Drug or IND filing). Those disease teams are working on diabetes, stroke, macular degeneration and ALS (also known as Lou Gehrig's disease).

A.A.

The Personhood Amendment: California here we come

2011-11-10T14:04:00.000-08:00

Sen. Art Torres (Ret.) is vice-chair of the CIRM governing board. His biography is available here.

A ballot measure that defined a fertilized egg as a person failed to pass in Mississippi on Tuesday. The amendments passage would have restricted stem cell research, and the Washington Post reported on additional concerns caused by the measure:

Opponents say that measure could have criminalized birth control, affected in vitro fertilization practices and even forced doctors to decline to provide pregnant cancer patients with chemotherapy for fear of legal repercussions.

A substantially similar measure failed twice in Colorado by 2:1 margins.

The Mississippi and Colorado measures are a concern for the stem cell community because of their impact on patients, scientist and the public. By criminalizing the creation of embryonic stem cell lines, these laws restrict research in their home state and outside as well. For example, CIRM researchers have turned away donors residing in states with laws that criminalize the creation of stem cell lines from surplus IVF embryos. These restrictive laws frustrate prospective donors by limiting their options.

As Jonathan Moreno points out on Science Progress,

“the Mississippi movement will not be the last.”

In fact, a personho proposal has already been submitted in California. According the legislative analysis:

"this measure could restrict stem cell research and alter medical practices in both the public and private sector."

CIRM plans to prepare an objective analysis of the effect on the proposed measure on stem cell research in the near future.

Art Torres

Lights…Camera…Stem Cells! Filming the 2011 CIRM Grantee Meeting

2011-11-10T10:28:00.000-08:00

Todd Dubnicoff is CIRM’s videographer and video editor

No family reunion is complete until somebody brings out the video camera. Our CIRM family is no different. So my colleague Amy Adams and I went on-location to downtown San Francisco in mid-September to film the 2011 CIRM Grantee Meeting. This almost annual, three day event brings together the California stem cell scientists and trainees who receive CIRM funding (several international collaborators were also in attendance as well as out-of-state guest speakers).

Though the scientists produce research results back in their labs at their home institutions, getting the chance to discuss those results in person with fellow stem cell researchers can spark new discoveries. Eugene Brandon of ViaCyte, Inc. explained that:

One of the great things about the CIRM Grantee Meeting is that I can meet with other people that are working on related research that I wouldn’t necessarily come across otherwise. In talking to these people, sometimes our team gets ideas that we could add to our work that might make our work better; that might make the product we’re working on better.

Face-to-face meetings also foster new collaborations. As Dennis Clegg of UC Santa Barbara pointed out:

"There are lots of opportunities to network and establish collaborations. A lot of the collaborations that we have going were established at this meeting”

To capture the palpable excitement of the event on film, we roamed the meeting hall to record quick “person-on-the-street” video interviews with several CIRM grantees. Most scientists aren’t particularly eager to jump in front of the camera lens, but once the videotape began rolling they delivered impressive impromptu responses. We interviewed graduate students, postdoctoral fellows, and senior scientists about their work developing therapies for a wide range of diseases.

To create the video I distilled 100 minutes of footage down to three-minutes that capture the mood and excitement of the meeting. I think it highlights well how our extended CIRM family is working together to accelerate the development of stem cell based treatments for chronic disease and injury. Pat Olson, CIRM’s Executive Director of Scientific Activities, summed it up best:

When scientists work together it helps move the science forward faster and ultimately that benefits patients and science”

And just like your typical family reunion, everyone was sad to say their goodbyes and yet they were excited to return home to try out that new “recipe” idea, and they looked forward to the next get together.

Note: In addition to the 3-minute piece, you can also view eight bonus videos from the meeting that give slightly more detailed explanations of various CIRM-funded projects. Also, last month we posted video recordings of Craig Venter’s keynote address and John Wagner’s closing scientific talk. Video of the Target Product Profile Workshop that was led by Ellen Feigal, CIRM’s Senior VP of R&D, will be posted soon.

Neurons made from embryonic stem cells treat Parkinson's disease symptoms in animals

2011-11-09T09:42:00.000-08:00

Last weekend Nature published a paper showing that nerve cells derived from embryonic stem cells can treat symptoms of Parkinson's disease in mice, rats and monkeys.

The scientists, who were from Memorial Sloan-Kettering Cancer Centre in New York, started with embryonic stem cells. They matured those cells into precursors of the ones that disappear in people with Parkinson's disease — so-called dopiminergic neurons. This step was hard-won. The Guardian quotes the lead author talking about the development:

"Previously we did not fully understand the particular signals needed to tell stem cells how to differentiate into the right type of cells," said Dr Lorenz Studer at the Memorial Sloan-Kettering Cancer Centre in New York.

"The cells we produced in the past would produce some dopamine but in fact were not quite the right type of cell, so there were limited improvements in the animals. Now we know how to do it right, which is promising for future clinical use."

Discover Magazine described how they tested the cells:

The researchers then injected over 100,000 of these newly grown neurons into the brains of mice that had a rodent equivalent of Parkinson’s disease: damaged dopamine-producing cells and the resulting difficulties controlling muscle movement. Over the course of three to five months, the transplanted neurons thrived, connecting with surrounding brain cells, and the mice’s motor function greatly improved. When the team repeated the experiment in rats, the result was the same: A few months later, the stem cell-derived neurons had integrated into the brain and the rats were moving around just fine.

This technique produced enough neurons that the researchers were able to inject two rhesus monkeys with Parkinson’s-like damage with 7 million new dopamine-producing brain cells each, far closer to the number a human patient would need. A month later, the transplanted neurons were alive and well in the monkeys’ brains—though it was too early to tell whether the new neurons would restore normal movement.

Maturing embryonic stem cells into a cell type that can be transplanted to treat Parkinson's disease has been one of the great hopes for the field of stem cell research. There is currently no treatment for the 500,000 people living with Parkinson's disease in the U.S. CIRM has invested almost $40 million into 20 projects aimed at developing stem cell-based therapies for the disease. (You can see a complete list of those awards here.)

Scientists still have the difficult task ahead of providing evidence to the Food and Drug Administration that these cells are safe to test in human trials. Even then, humans are quite different from mice, rats and even monkeys and there is no way of predicting whether a therapy that works in animals will be similarly successful in humans. The Guardian quoted Studer discussing the future of this research:

"We now have the right cells, but to put them into humans requires them to be produced in a specialised facility rather than a laboratory, for safety reasons. We have removed the main biological bottleneck and now it's an engineering problem."

A.A.

Kids lined up shoulder-to-shoulder to create stem cells

2011-11-08T09:31:00.000-08:00

Kids made embryonic stem cells out of Play Doh at the Bay Area Science Festival.

It was fun waking up yesterday morning to the headline in the San Francisco Chronicle "Science fair hits it out of the park." It was a bit of an obvious headline because on Sunday 21,000 people had come to AT&T Park, home of the San Francisco Giants, for the last event of the 10-day Bay Area Science Festival. CIRM was one of more than 170 organizations to provide hands-on science opportunities for kids and their parents at the event.

We took an activity from our five-module online high school curriculum (the full curriculum is here) and adapted it for the younger audience at the science festival. We had them use Play Doh to walk through the first five days of development and build a blastocyst where we could show them how to harvest stem cells using a turkey baster instead of a pipette. Depending on the age of the child, a few steps and a few big words were left out. But all ages got it when we told them we liked stem cells because they could help repair daddy (or mommy depending on who was standing behind them) if he was broken.

A group from the UC Berkeley Student Stem Cell Society ably kept the kids entertained while I and my colleagues from CIRM talked to the parents about CIRM results to date. They were uniformly excited about the 44 projects that are in various stages of working toward therapies for 26 diseases (that list of projects and information about their status is available on our web site).

Having a very well worn personal soap box about science literacy, it was thrilling to see so many families out, and seeing them getting into understanding the science at each of the stations. Kishore Hari, one of the festival organizers from UCSF, said the same thing to the Chronicle's David Perlman:

"Kids and their grownups too are spending real time at all the exhibits, and they are really working the experiments. I can see a real hunger for science all around me and it is uplifting"

In full disclosure, Dave Perlman was a mentor of mine when I first started as a science writer, as he was to most of my generation of science writers. I just wish American media outlets had room for more like him, we would be a bit further down the road to science literacy.

D.G.

Forming industry partnerships, ensuring new therapies reach patients

2011-11-07T08:44:00.000-08:00

At our governing board meeting on October 26, the board approved a $30 million initiative that will be critical for making sure that research funded by CIRM eventually makes it to patients.

In the past year, CIRM has begun funding early phase clinical trials for stem cell-based therapies. These early phase clinical trials are done to make sure that the prospective therapy is safe, and can also show preliminary evidence that it may be effective. What we don't fund are the large, later phase clinical trials that the Food and Drug Administration requires to confirm whether or not the therapy is safe and effective before approving a new therapy for patients. (This resource has information about the stages of therapy development.)

These large clinical trials cost a lot of money, and conducting these trials can benefit from the kinds of expertise that industry partners can provide.

Ideally, what would happen is that CIRM would fund the research leading up to FDA approval to begin a clinical trial, and we'll fund some early phase trials (or provide matching funds through a loan, such as the Geron trial we're supporting now). For trials that start with investigators in universities, or in small companies, larger industry partners would then have the opportunity to help fund the early trials and would pick up any project that succeeded in early trials and carry out the expensive later-stage confirmatory trials.

The new $30 million Strategic Partnership Funding Program will promote the partnerships between academic groups or small businesses and the larger industry partners whose participation will be critical for carrying out the late-stage clinical trials. Forming those relationships also provides our grantees with a source of advice that can help them design their early trials and overcome regulatory hurdles.

Elona Baum, CIRM General Counsel and Vice President of Business Development, led the effort to develop this fund. She said:

“With this fund we want to make sure that CIRM grantees get early access to the expertise of biopharmaceutical companies who will then, at Phase III, bring the project through the goal line. We want to increase the likelihood that CIRM research has access to funding in the later stage of development which is critical to ensuring it gets into the market place and helps patients in need. We're being proactive by engaging industry early in the process of developing new therapies.”

This Partnership fund is one portion of an overall Opportunity Fund. The two other parts of that fund will be presented to the board for approval in December or January. Together, the funds are designed to keep CIRM nimble and looking ahead to the resources and expertise our grantees will need in the future if our funding is going to be a success.

A.A.

Guest blogger Alan Trounson — October’s stem cell research highlights

2011-11-04T08:34:00.000-07:00

Each month CIRM President Alan Trounson gives his perspective on recently published papers he thinks will be valuable in moving the field of stem cell research forward. This month’s report, along with an archive of past reports, is available on the CIRM website.

This month’s lead story garnered considerable media attention. A team at the New York Stem Cell Foundation succeeded in creating embryonic stem cell lines through nuclear transfer, sometimes called cloning. The actual science of what the group did has already been covered in this blog (read the blog entry here). Now, I am suggesting that, because the trick they used to get the cloning to work resulted in cells with three sets of chromosomes, the follow-on research that tries to understand why their method worked may produce much more useful data than the original breakthrough. I look forward to reading those next papers.

October also produced another salvo in the back and forth over how useful iPS cells— the stem cells that result from reprograming adult cells—really are. Early this year, a few papers appeared suggesting iPS cells had considerably more genetic defects than their embryonic counterparts. Now a team at Scripps and University of Virginia using a somewhat different reprogramming technique, and a 30-fold better method of gene analysis, found almost no gene defects attributable to the reprogramming. The last chapter in this saga is far from being written.

At a time when it seems like teams announce the full gene sequences of another animal or bacteria weekly, saying that a paper on gene sequencing is important to our field may appear to be a stretch. However, when BioTime announced that they had sequenced five of their clinical grade embryonic cell lines, it did allow us to tick the box on an important milestone for our field. Many observers believe the FDA may start to demand some sort of evidence of the genetic integrity of cell lines that are going into clinical trials. So, having these lines available could indeed accelerate our pace to the clinic.

I hope you find my full report on this month's science picks interesting.

- Alan Trounson

Fly stem cells give insights into aging and longevity

2011-11-03T14:26:00.000-07:00

Yesterday brought news about stem cells in older people. Today, there's news by CIRM grantees about how a single gene alteration in a stem cell can help keep an entire organ more youthful -- at least in flies.

The work was by a team of researchers at the University of California, Los Angeles, the Salk Institute for Biological Studies and the University of California, San Diego. It all started with a long-known observation: cutting calories in many laboratory animals can also dramatically extend the animal's life. This is true in common lab animals such as flies, worms, and mice, and also holds true in primates.

In addition to living longer, those hungry, long-lived animals have more of the energy-producing cellular structures called mitochondria. The researchers were curious if simply boosting the number of mitochondria without all that painful hunger would work the same trick. One known way of boosting mitochondria is to rev up a protein called PGC-1.

A press release from Salk describes the work of associate professor Leanne Jones' work like this:

"This chain of connections between the mitochondria and longevity inspired Jones and her colleague to investigate what happens when the PGC-1 gene is forced into overdrive. To do this, they used genetic engineering techniques to boost the activity of the fruit fly equivalent of the PGC-1 gene. The flies (known as Drosophila melanogaster) have a short lifespan, allowing the scientists to study aging and longevity in ways that aren't as feasible in longer-lived organisms such as mice or human."

The researchers specifically bumped up the PGC-1 gene in stem cells that line the fly intestine. They found two things: 1) those fly intestine stem cells had more mitochondria, and 2) the flies lived a lot longer than their unaltered lab-mates. All that, with no starvation.

Here, I should pause to say that if you think your intestine is so different from a fly's you'd be wrong. Their intestine is lined with stem cells not unlike our own, and those cells function in a very similar way using similar genes. That's not to say that all research in flies directly translates to humans, but it is a pretty good model for testing out ideas.

Jones, who has a New Faculty award from CIRM, had this to say in the press release about the findings:

"Slowing the aging of a single, important organ - in this case the intestine - could have a dramatic effect on overall health and longevity," Jones says. "In a disease that affects multiple tissues, for instance, you might focus on keeping one organ healthy, and to do that you might be able to utilize PGC-1."

This research is in the very preliminary stages and is far from being ready for an human use. However, it's this kind of basic discovery that continuously fuels new ideas for human therapies.

CIRM Funding: Leanne Jones (RN1-00544-1)
Cell Metabolism, November 1, 2011

- A.A.

Older stem cells returned to youth

2011-11-02T10:13:00.000-07:00

We've written quite a bit about research by CIRM grantee Irina Conboy at the University if California Berkeley (blogged here), who has found that the muscle stem cells in older people don't respond as enthusiastically to repair muscle damage — much to the dismay of aging athletes. What they've also learned is that environment is key. Those same sluggish stem cells respond more rapidly when bathed in younger blood, at least in mice. Their work suggests that the muscle stem cells are still effective, it's the older surrounding cells that are the problem.

New research by a group at the University of Texas Health Science Center San Antonio has found something similar with stem cells that produce bone. They took mesenchymal stem cells from the bone marrow of mice. These cells are different than the blood-forming stem cells also found in bone marrow, which continuously form all cells of the blood system. The mesenchymal stem cells are bone marrow residents that can make bone, cartilage and fat, among other tissues.

The research, published in the FASEB Journal in May, showed that mesenchymal stem cells (MSCs) from old and young mice both multiplied four times more when grown in the lab on cells taken from younger mice versus older mice. What this means is that even though the tissue-specific stem cells might not be very active in an older body, those cells can be given a new lease on life in the lab. A press release from UT Health Science Center quotes the senior author on the work:

“The number and quality of those cells decline with age, that is very clear,” said Xiao-Dong Chen, M.D., Ph.D., a stem cell researcher at the UT Health Science Center. “And, using the patient’s own cells can impact results.”

This work was in mice, which means that it may or may not translate to humans. But this kind of research is important, given that many stem cell-based therapies that CIRM and others are funding address diseases that occur in older people with older stem cells. Knowing how to return those stem cells to a more youthful state could be important for developing effective therapies of aging.

- A.A.

Vampires get a taste of lab-grown blood

2011-10-31T14:16:00.000-07:00

Good news for vampires and patients alike: Scientists in Edinburgh have generated red blood cells directly from bone marrow stem cells in the lab. This alternate source of cells could help the 4.5 million people in the U.S. who need a transfusion each year (from America's Blood Centers, which has many interesting facts about how much blood is needed and how little is donated).

Wired writes:

Professor Marc Turner, who leads the team, believes the blood could be ready for trials in as little as two years, once it's married with research producing artificial haemoglobin -- the protein responsible for transporting oxygen in the blood of vertibrates.

The team are working to produce blood type O-negative, which is good news, as that's the type that 98 percent of us can accept. Because it's essentially manufactured, it would be guaranteed to be free from any viruses and diseases, like HIV, Hepatitis and vCJD (mad cow disease).

The Telegraph quotes Turner, who led the project:

"I think it will probably be two or three years before we get to clinical trials and I would think it will be a decade or so before one sees these kinds of artificial red cells or cultured red cells in routine general practice."

- A.A.

State-of-the-Art Science and Architecture combine for a World-Class Downtown

2011-10-28T12:47:00.000-07:00

Erin Rhoades is a professional city planner and lifelong Berkeley resident. Ms. Rhoades' planning interests are focused on infill development and sustainability. Erin is a founding Board member of Livable Berkeley and the Board Chair.


The Li Ka Shing Center for Biomedical and Health Sciences/ University of California, Berkeley

The Li Ka Shing Center for Biomedical and Health Sciences, dedicated last week, stands at the nexus of downtown Berkeley and the University of California, Berkeley campus. The center is symbolic of a vision, not just for UC Berkeley, but the community as a whole. This building is the eighth of twelve stem cell research facilities funded in part by CIRM to open its doors (read more about CIRM's major facilities).

From the standpoint of design, the building incorporates a range of environmental features. The materials and energy efficiency are state-of-the-art, including a living roof. Architecturally, the center incorporates contemporary design and finish into a space surrounded by structures of historic significance and natural green space.

These design features are thoroughly consistent with the Downtown Area Plan's (DAP) goals for LEED Gold or equivalent development with outwardly visible sustainable design features that display innovation in green architecture in the context of a downtown with a predominanlty historic character.

Robert Birgeneau,
Chancellor of UC Berkeley,
at the dedication ceremony

Inside, the center will be home to student scientists at every level of education working to tackle emerging and neglected diseases of national and international significance. The flexible and open design will facilitate collaboration among these teams.

The $257 million facility, which received $20 million from CIRM, was financed through an innovative public private partnership involving state bond funds, individual donors and foundations. This model of combining public investment with private funds serves to leverage tax dollars and accelerate benefits to taxpayers.

Innovative funding approaches, like those used to construct the Li Ka Shing Center and the other CIRM major facilities, will be required in Berkeley to achieve the magnitude of investment necessary for high-density infill development and at the same time to accomplish the affordable housing component, community benefits and streetscaping called for in the DAP.

The combination of creating state-of-the-art development, supporting the knowledge (“imagined in California”) economy through public / private financing is an important model for the City of Berkeley. As we move into the 21st century, Berkeley should build on these success stories and support development that builds on this innovative model.

Development in downtown Berkeley should look for ways to showcase the best thinking in progressive environmental design and urban culture. Buildings like the Li Ka Shing Center and the David Brower Center, including their programmatic functions, exemplify Livable Berkeley's advocacy for a "world class" downtown. Our hope is that the Downtown Area Plan will result in the next building that defines Berkeley not for where it's been, but where it's going.

Erin Rhoades

Peyton Manning and how a political football goes flat

2011-10-27T12:48:00.000-07:00

Jonathan Moreno is senior fellow at the Center for American Progress and the David and Lyn Silfen University Professor at the University of Pennsylvania.

In a cleverly written but factually empty blog post, Tony Perkins of the Family Research Council tries to justify his organization's opposition to human embryonic stem cell research. This time he avers to the decision of the National Football League's Peyton Manning to resort to adult stem cell treatments in Europe because, Perkins tells us, "the U.S. is giving preferential treatment to embryonic stem cell research." This assertion is simply false, and I challenge Perkins to provide the evidence. In fact, nationally far more has been spent on adult stem cell research than embryonic.

Perkins also argues that Peyton's decision to go to Europe to have some of his own fat cells injected into his neck "has impacted the debate" on adult stem cell research. I'm not sure what impact or debate he's referring to. He's absolutely right that "[i]t's too early to tell if the treatment's had any impact on Manning's neck," but he seems far more excited about the debate than whether the "treatment" actually works. At this time there is no evidence that the treatment Manning seeks is more beneficial than potentially harmful. The injection of potent cells into the body is not necessarily a benign procedure, which is why the U.S. Food and Drug Administration is being so careful about reviewing these proposals, both for adult and embryonic stem cell procedures.

Perkins operates on a transparent double standard. It's also "too early to tell" whether embryonic stem cell research will be of medical benefit, which is precisely why the work is being done, but that criterion only seems to apply when it's consistent with Perkins' real agenda. Intellectual honestly requires Perkins to acknowledge that he is opposed to research involving human embryos, regardless of potential benefit. That is a respectable position that shouldn¹t be painted over by sophistry. So is Manning's decision to seek relief where he can, but that decision should be accompanied by an awareness of the risks and the lack of evidence of benefit.

Procedures like the one Manning wants should be approached as carefully controlled research studies with full informed consent and prior review by an independent ethics board. Then perhaps we will know if future patients can expect some relief, or if they are just writing a check and exposing themselves to unwarranted risks.

What is striking about debates like that over human embryonic stem cell research is the way that they continue to be fodder for cultural division. This is something new in the role of science in America, and seems to be especially prevalent in biology. I write about the "new biopolitics" in my latest book, "The Body Politic: The Battle Over Science in America" (Bellevue Literary Press, 2011). Esoteric bioethical and scientific questions like stem cells and cloning have become part of the political process. There is no reason to think that these issues will recede from the political debate; indeed, they have already surfaced in the current presidential election cycle.

But they also create somewhat unpredictable responses from those who would normally identify themselves as on the left or right, as worries about the impressive results or at least the symbolism of experimental biology cause understandable concern about the implications of powerful new science. There are good reasons to think about these issues in fresh new ways. But the same old predictable rhetoric doesn't help us do that.

Jonathan Moreno

Purified heart cells from human embryonic stem cells

2011-10-26T10:34:00.000-07:00

Earlier this week, a team from South San Fransisco-based VistaGen and Toronto's McEwen Centre published a paper in the October 23, 2011 Nature Biotechnology that could have important consequences for efforts to repair heart attack damage with stem cells. VistaGen has a CIRM Tools & Technologies award, though that award did not fund the work published this week.

The team, which was led by Gordon Keller at the University Health Network’s McEwen Centre for Regenerative Medicine in Toronto, developed a way of maturing embryonic stem cells into early heart cells and purifying them. They did this by first discovering a protien that's on the surface of early heart cells. They could then use antibodies to keep only those cells that have the protein and eliminate all cells without the protein. Creating pure populations of cells is critical for developig therapies, which need to be free of the original embryonic stem cells that can form tumors.

A press release from VistaGen described the technology:

These findings provide, for the first time, a simple method for isolating some of the earliest populations of cardiac precursors and mature cardiomyocytes from human pluripotent stem cell cultures. This readily adaptable technology offers a viable approach for generating large numbers of enriched, non-genetically modified, cardiomyocytes for numerous therapeutic applications.

Creating pure populations of cells is just the first step. Before the cells are shown to be therapeutically useful they must be able to integrate into the complex three-dimensional structure of the human heart and beat in time with the surrounding tissue.

A.A.

The European embryonic stem cell patent ban: The Other Side of the Coin?

2011-10-25T09:23:00.000-07:00

Geoff Lomax is CIRM's Senior Officer to the Standards Working Group

Last week we posted on the initial views of scientists and policy analysts on the 10/18 European Court of Justice decision regarding the patentability of hESC products. The initial views were quite pessimistic with regard to hESC-based therapy development, although James Lawford-Davies did offer a few rays of hope for the field.

This week Nature published a piece suggesting there may be a "silver-lining" to the decision. Some commentators believe companies may focus on patents covering the tools and technologies as opposed to cells and their biological products. Further, the absence of a 'patent thicket" may speed therapy development by reducing the chance of infringement of intellectual property rights.

Nature quotes physician scientist Chris Mason of University College London:

"If anything the ruling is an opportunity. It's not the end of stem cells in Europe."

The piece goes on to explain that even a restrictive interpretation should allow companies to patent new and innovative technologies needed to turn human ES cells into treatments. The goal becomes patenting the innovative tools, rather than patenting the cells themselves.

"If the sum total of this market were some cell lines, I would be deeply, deeply worried," says Julian Hitchcock, a life-sciences lawyer at Field Fisher Waterhouse in London. Growth media, equipment and chemicals that help scientists to work with stem cells could all be patented in Europe without running afoul of the high court's ruling, he says.

In addition to debate over the ruling's long-term effects, there is some uncertainty over which cell types would fall under the ruling. Advanced Cell Technology, based in Marlborough, Mass., has developed a technique to create embryonic stem cell lines that does not destroy the embryo. They've issued a press release indicating that their cell lines would not be covered by the ban. They write:

”This is a huge setback for stem cell research in Europe,” said Robert Lanza, M.D., ACT's chief scientific officer. “However, the Court went out of its way to stress that inventions are unpatentable if they ˜necessitate' the destruction of human embryos. Therefore, this ruling does not appear to affect our single-blastomere technology, which does not require the destruction of embryos at any point. We will do whatever we can to ensure that therapies derived using these stem cells are made available to the patients in Europe who need them.”

G.L.

Bakersfield residents learn about stem cell progress in aging, macular degeneration

2011-10-24T11:50:00.000-07:00

This weekend CIRM hosted an educational event in Bakersfield to update people on the progress being made by CIRM grantees. The event featured a keynote address by board chair Jonathan Thomas plus talks by grantees working on age-related diseases including blindness.

Although CIRM holds board meetings throughout California, this is the first time people in Bakersfield have had a chance to hear directly from CIRM. If media attention in advance of the meeting is anything to judge by, the local community was excited about hosting us. The local radio station KERN spoke with CIRM patient advocate coordinator Chris Stiehl, who helped organize the event. You can listen to that interview here.

Among other things, Stiehl discussed the Geron spinal cord injury trial as one sign that the field of stem cell research is progressing.

"Geron Corporation is doing clinical trials with stem cells on people with spinal cord injuries. That's amazing. We never had anything for those people except wheelchairs and someday they may get out of their wheelchairs because of this."

The Bakerfield Californian also had a nice piece announcing the event.

As with all CIRM patient advocacy events, if you can't make the event you can follow the discussion on Twitter either by watching the stem cell conversation on #stemcells or by following the event's hash tag, which is listed on the agenda on the CIRM web site. There's another event coming up October 29 in Santa Rosa, which you can follow at #CIRMSantaRosa.

These types of public events featuring CIRM scientists and patient advocates are going to be ongoing throughout the state as a way of making sure the people of California get a chance to learn about progress being made by the institute.

You can get more information about all the awards CIRM has funded and which institutes have received funding on our website.

A.A.

CIRM grantees at Gladstone Institute receive $5 million to expand stem cell program

2011-10-19T11:55:00.000-07:00

The Gladstone Institutes in San Francisco are set to expand their stem cell research program with a $5 million gift from the Roddenberry Foundation.

The independent Institute, which is associated with the University of California, San Francisco, has received $24 million in funding from CIRM (you can see a complete list of those awards here). The 14 awards fund training new stem cell scientists, creating a lab facility where Gladstone scientists can share stem cell resources and awards to aid in creating reprogrammed stem cells (known as iPS cells) and treat cardiovascular diseases and HIV/AIDS, among others.

The Roddenberry gift will expand these existing areas of expertise among Gladstone scientists by creating the Roddenberry Center for Stem Cell Biology and Medicine - named after Gene Roddenberry, who created "Star Trek".

A story by Erin Allday at the San Francisco Chronicle quotes Rod Roddenberry, Gene Roddenberry's son:

"We don't fool ourselves into thinking we're going to cure Alzheimer's or heart disease overnight, but if they tell us they are breaking ground and moving forward, we definitely want to help them do it."

"It was amazing to go up to Gladstone and look through a microscope and see a sheet of beating heart cells, and know they came from skin cells," Roddenberry said. "Walking around the institute, we met scientists who were passionate and excited by what they were doing. And as corny as it sounds, a lot of them believed in the 'Star Trek' future, a beautiful future."

Allday also spoke with CIRM President Alan Trouson about the Gladstone Institutes:

"Gladstone is small, but it's incredibly effective, and it's ranked very high by scientists around this country as one of the best institutes."

A press release from the Gladstone Institutes about the gift quotes Deepak Srivastava, who directs both stem cell and cardiovascular research at Gladstone:

“Today's biggest challenge for solving disease is getting the investments required to transform our basic-science discoveries into health solutions that can alleviate human suffering.”

Investments like those from CIRM and now the Roddenberry Foundation should help accelerate the translation of basic discoveries by Gladstone scientists into real therapies. This video discusses work by Gladstone scientist Bruce Conklin, who is developing a stem cell method of screening drugs to treat a form of heart disease:

A.A.

Experts View European Court Ruling as a Setback for Stem Cell Therapies

2011-10-18T09:39:00.000-07:00

Geoff Lomax is CIRM's Senior Officer to the Standards Working Group

The European Court of Justice issued a ruling today that therapeutic products created from human embryonic stem cells are not patentable. A press release cites the court's decision:

Court holds that an invention is excluded from patentability where the implementation of the process requires either the prior destruction of human embryos or their prior use as base material, even if, in the patent application, the description of that process, as in the present case, does not refer to the use of human embryos.

James Lawford-Davies presented background on the case at the World Stem Cell Summit October 5 in Pasadena. He says the decision is seen as "a victory by those opposed to the use of embryos for research in the EU". Aurora Plomer, a legal scholar at the University of Sheffield, concurs:

"The ruling of the Court of Justice of the European Union could be in breach of the European Convention on Human Rights in failing to recognize the margin of discretion granted to Member States on the rights of human embryos."

Researchers are equally disappointed. An AP story quotes Pete Coffey, who received a CIRM Research Leadership Award to support his move from University College London to the University of California Santa Barbara. Coffey has been developing an embryonic stem cell-based approach to treating the most common form on blindness.

"This is a devastating decision which will stop stem cell therapies' use in medicine," Pete Coffey, a stem cell researcher at University College London, said in a statement. "The potential to treat disabling and life-threatening diseases using stem cells will not be realized in Europe."

The Guardian quotes Austin Smith, head of the Wellcome Trust Centre for Stem Cell Research at Cambridge University, who said that the decision left European scientists is a "ridiculous position".

"We are funded to do research for the public good, yet prevented from taking our discoveries to the market place where they could be developed into new medicines. One consequence is that the benefits of our research will be reaped in America and Asia."

Lawford-Davies says he still holds out hope for the field for the following reasons:

Inventors and patent attorneys have known about this concern for some time and have been drafting to try to take account of the court position.
It should be possible to obtain patents on allied technologies, such as biomarkers and diagnostics related to the particular therapy.
It is still possible to obtain these types of patents in most other countries in the world, including the US.

G.L.

CIRM high school curriculum a hit in the land of Disney

2011-10-17T12:09:00.000-07:00

CIRM took our high school curriculum on the road last week to the annual meeting of the National Association of Biology Teachers in Anaheim at a hotel just down the block from Disneyland. About 800 biology educators attended the meeting. Although I did not venture into the amusement park, I suspect the exhibit hall at the conference had some equally fanciful attractions such as the 3-D video anatomy display across the aisle from the CIRM booth and the virtual tour of a Costa Rican rain forest. So, I was initially a bit concerned about how stem cells would compete for the teachers' attention. That concern was pretty quickly set aside.

At the very beginning of the meeting we had a CIRM hands-on workshop to walk a room full of teachers through how our five on-line modules and introductory lesson can be used. You can find them all here. Many in the room walked away after the hour session saying they planned to use the curriculum.

The next day the exhibit hall opened and we had a steady parade of teachers coming by to say their students had been asking about stem cells and that they were thrilled to find out that such a robust curriculum was available on the web and seemed a bit shocked and pleased to find out it was completely free. They liked that each module had student resources and teacher resources, glossaries and assessment tools. Many talked about dressing up their classrooms with blow-ups of the images CIRM has linked off the curriculum and on our Flickr site.

Three days later as the meeting was winding down on Saturday, one teacher who had come by to chat the first day dropped by again to say, "I just wanted to tell you, you are the best thing in this place."

With that I would like to offer kudos to the team from U.C. Berkeley and the Bay Area high school teachers that helped us build the five modules, and particularly to thank Laurel Barchas who managed the project.

D.G.

Researchers fix mutation in reprogrammed stem cell, create functional liver

2011-10-14T15:04:00.000-07:00

A group led by the Sanger Institute and the University of Cambridge, working with the Sangamo Biosciences, has shown that it's possible to fix mutations in reprogrammed cells. This work, which was published in Nature, takes two previous advances and combines them into one proof-of-concept.

Since 2007 stem cell scientists have been able to reprogram adult cells such as skin back into an embryonic-like state. These so-called iPS cells can then mature into any cell type in the body, much like embryonic stem cells.

Other groups have shown that it's possible to take adult stem cells such as those from the bone marrow, correct mutations, and create mutation-free cells that, at least in animal models, can fix diseases. That's the idea behind CIRM's two HIV/AIDS disease team awards (described here and here) and a sickle cell disease team. In fact, one of the HIV/AIDS disease teams is also working with technology developed by Sangamo to fix the mutations.

In the work reported in Nature, the team created iPS cells from a person with a genetic liver disease, fixed the mutation, then matured the iPS cells into functional liver cells. A Reuters story quotes Allan Bradley, director of the Sanger Institute:

"These are early steps, but if this technology can be taken into treatment, it will offer great possible benefits for patients," he added.

Reuters quoted David Lomas, who was part of the team from Cambridge, saying that the liver cells survived when transplanted into mice.

The researchers said it could be another five to 10 years before full clinical trials of the technique could be run using patients with liver disease. But if they succeed, liver transplants -- costly and complicated procedures where patients need a lifetime of drugs to ensure the new organ is not rejected -- could become a thing of the past.

"If we can use a patient's own skins cells to produce liver cells that we can put back into the patient, we may prevent the future need for transplantation," said Lomas.

A.A.

Patient advocates report in on the World Stem Cell Summit

2011-10-12T09:24:00.000-07:00

These past few days post-World Stem Cell Summit has seen a lot of activity online from patient advocates who attended the meeting. One goal of that meeting is specifically to update the advocates on what's happening in stem cell research and also empower people to speak up about the value of the research. Bernie Siegel, who organized the meeting, seems to have succeeded if the number of advocates writing blog entries about his meeting is any indication.

Don Reed wrote a summary of his experiences at the meeting on his blog Stem Cell Battles. Reed was on a panel with me, Paul Knoepfler from UC Davis, and John Hlinko of Moveon.org and Left Action talking about how to use social media for stem cell advocacy. Reed wrote about the need for advocates to have answers at the ready:

For example, if someone says, “We can’t afford to fund stem cell research,” we immediately answer, “We can’t afford NOT to”—and it helps to have a few basic statistics handy, such as:

In 2009, America spent $1.65 trillion on chronic (incurable) disease. This is more than all federal taxes ($1.2 trillion) put together. It even exceeds that year’s installment of the national debt ($1.60 trillion). No nation can afford such costs—and it is why the economy is going down.

You can find some quick answers to common misconceptions about stem cell research in our stem cell basics.

Knoepfler has taken on the unusual role of stem cell scientist and patient advocate (he survived prostate cancer). He now has a blog about the science of stem cell research that he promotes through both Twitter and Facebook. He is a strong advocate for scientists speaking out and not being afraid to voice a public opinion about the value of research. On his blog, Knoepfler wrote:

Today I was part of a panel discussion on social media for the stem cell cause at the World Stem Cell Summit

…

Something that one of speakers said in the session that ended right before ours stuck with me as I was giving my talk. This person said that as part of the multi-dimensional team advocating for stem cell research that:

Scientists should just stick to the facts.

I like facts (aka data) as much as the next guy, but when it comes to advocating for stem cell research, my opinion is that scientists need to go beyond facts. We need to use our authority to voice opinions.

One point all three of us made is that whether you are a scientists, a patient or a member of the public who cares about finding new therapies it's important to get your voice heard by writing your legislators, talking to friends or family members and sharing information about stem cell research through conversation, emails, facebook, twitter or in blogs.

One advocate who is on board with that message is Karmel Allison who wrote about her experiences at the World Stem Cell Summit on the blog A Sweet Life. She said:

At the conference, I heard about amazing progress being made towards modeling neurological disease, regenerating heart tissue, growing kidneys, and even curing HIV. Even with so many stem cell applications to talk about, though, diabetes was no small player, and I was surprised by how much I didn’t know about diabetes and stem cells.

I had heard about the hope for beta cell regeneration, in which stem cells would be differentiated into beta cells and implanted into diabetics so that we could essentially regrow our defunct pancreases. This source of beta cells would be far more renewable and therefore preferable to the current source– pancreases from cadavers, which are very hard to come by.

Allison also attended a talk by CIRM grantees at ViaCyte, who have a Disease Team Award to develop a stem cell-based therapy for diabetes. She wrote:

The challenge ViaCyte is aiming to overcome is that the stem cell development process needs to be done in a reliable, industrialized fashion such that it can be profitable. So, ViaCyte is using a stable, well-characterized line of human embryonic stem cells that are cultured for two weeks, differentiated into progenitor cells, frozen for transport if necessary, encapsulated in a biocompatible envelope, and, in theory, implanted. The envelope system is designed to protect the cells from immune rejection, thereby circumventing the need for genetic matching.

A.A

Video describes life with Huntington's disease, hopes for stem cell therapies

2011-10-10T11:00:00.000-07:00

The University of California, Irvine has begun posting video interviews with their stem cell institute director Peter Donovan (You can see all of those videos here.). Of the eight interviews, including ones with former CIRM board chair Robert Klein and leading UCI stem cell researchers, one of the most moving is with Huntington's Disease advocate Frances Saldana.

Saldana lost her husband, one daughter and two of her husband's brothers to the disease. Her two remaining kids have advanced Huntington's disease. She now has two grandchildren, both of whom have a 50/50 chance of having inherited the disease. In the UCI video Saldana says:

"This is not an illness that is going to go away once you lose your loved one. It's going to carry on through the generations. When they do inherit Huntington's Disease they will lose the ability to walk, to talk and to swallow and they will start to experience atrophy of the muscles which causes spasticity and a lot of pain. It's very painful."

Saldana spoke to the CIRM governing board about life with Huntington's disease back in 2007. Saldana is one of many of the passionate advocates for Huntington's disease who have spoken with the agency over the years and who have been tireless supporters of stem cell research.

"What I would hope for, if not a cure, is a treatment to alleviate human suffering for our families. I don't think stem cell research will provide a cure for my two other children, but I have two grandchildren and now they are vibrant and beautiful and I hope they have a full life ahead of them, but we need to have something for them if and when they might be carrying that mutant protein."

The agency currently funds five awards with a focus on the disease. You see a list of these awards, learn more about Huntington's disease, and watch a video CIRM produced about the disease on our disease fact sheet.

A.A

Stem Cell Awareness Day introduces high school students to heros

2011-10-07T13:10:00.000-07:00

Stem Cell Awareness Day on Wednesday brought scientists to close to 60 classrooms to deliver lectures on stem cell science and inspired events throughout the world, some of which are ongoing throughout October. (You can see a full list of events here.)

The Daily Pilot had a nice story on an event at University of California, Irvine, which brought more than 100 high school students into UCI's Sue and Bill Gross Hall. CIRM contributed $27.2 million to the construction of the building. In addition to stem cell labs, the building houses equipment to help people with spinal cord injuries regain strength. The story quotes one of the students who attended:

"It's nice to see our tax dollars go to something that actually helps people," said Brittany Jackson, a Trabuco Hills High School senior. "There's so much technology. You don't realize there's so much that goes into helping those less fortunate."

The story goes on:

Standing between a computer monitor showing color dyed stem cells under a microscope and a refrigerator growing stem cells, Christina Tu talked about why she and researchers do what they do.

One scientist is working with a bioengineer to generate cells that can help a baby recover from heart failure at birth. Tu, the stem cell core facility coordinator, moved into stem cell research from another field because of the possibilities.

"They must have this passion," she said. "A lot of times, outcome is negative. You have to overcome that to see what you want to accomplish."

Nancy Luke, a lawyer stricken with multiple sclerosis, encouraged the students to move science forward.

"What I have is the hope that [what UCI is studying] can cure MS," she said. "Researchers rock. And you guys will be the heroes."

That's what Stem Cell Awareness Day is all about: Exposing people to those heroes, and encouraging students to become heroes themselves.

A.A.

New cells lines made using “cloning” technique valuable for research

2011-10-06T14:21:00.000-07:00

Yesterday a New York Stem Cell Foundation team reported for the first time that they had created two new embryonic stem cell lines through a technique known as somatic cell nuclear transfer (SCNT), which is sometimes called therapeutic cloning. They reported their findings in the journal Nature.

SCNT is a third avenue for creating cell lines able to form all tissues in the adult body – called being “pluripotent.” Interestingly, SCNT borrows from the two other techniques used to date.

Pluripotent cell lines were first created by extracting them from 5-6 day old human embryos left over after in vitro fertilization – hence their name human embryonic stem cell lines.

Pluripotent cell lines were later created by reverting skin cells to a pluripotent state through a process called “reprogramming” – commonly referred to as induced pluripotent cells.

SCNT is a reprogramming method that involves the creation of an embryo as a first step. In this case, scientists took DNA from a human skin cell and placed it in a human egg, which they then stimulated to form a 5-6 day old embryo. In this environment, the DNA was reprogrammed to an earlier state and the resulting cells were extracted to create human embryonic stem cell lines.

The fact that SCNT-derived stem cell lines have so much in common with other forms of pluripotent stem cells has some opponents of the research asking why bother? Here’s why. CIRM held a conference in June 2010 to discuss the value of pursuing SCNT and posted a report on the findings in November, 2010.

That report suggests three areas where embryonic stem cell lines generated through SCNT would clearly be valuable in three ways:

Understanding how you reprogram any cell to become pluripotent could help us optimize the creation of iPS cells, which are so far inefficient to create in addition to being incompletely reprogrammed.
Understanding and treating the rare diseases that are passed on from those few genes that reside outside the nucleus in the cellular organ called the mitochondria.
Studying the very early stages of human development, which are poorly understood now, and which is when some human diseases are thought to originate.

The fact that the New York team got the technique to work in humans is a significant advance that has value for all three of those potential areas of research. However, the two cell lines reported yesterday aren’t exactly ready for therapies. Rather than having two copies of each gene, as all of us do, these cells have three copies of every gene and are therefore biologically abnormal. The Wall Street Journal described the problem like this:

While such cloning experiments have been successful in various mammals, the "de-nucleated" egg approach hasn't worked so far in humans. Now, Dr. Egli and his colleagues have—partially—achieved it via a simple move: They didn't remove the egg's own nucleus.

Not removing the egg’s nucleus resulted in the triple copy of chromosomes (one from the egg and two from the donor’s nucleus) that left the cells as “research only” cell lines. Many news stories about the work have referred to the new lines as coming from “cloned embryos”. However, because the cell lines contain more chromosomes than the donor cell they are not truly clones.

Understanding what factors in the nucleus aided in getting SCNT to work could provide clues about factors that might aid in making iPS cells more efficiently, and also provide clues as to how to create SCNT-derived lines with normal numbers of chromosomes.

The Wall Street Journal story quotes George Daly, a stem-cell researcher at Children's Hospital Boston , who summarizes the findings as “a landmark even if it isn’t a complete victory.”

In coming months we should watch for advances that turn this landmark into a victory for people hoping to use the SCNT-derived stem cells to study the earliest stages of development, understand and treat mitochondrial diseases, and learn how to create better iPS cells.

Guest blogger Alan Trounson — September’s stem cell research highlights

2011-10-05T11:00:00.000-07:00

CIRM video journal of the World Stem Cell Summit

2011-10-04T09:30:00.000-07:00

The World Stem Cell Summit is going on now in Pasadena. This is the primary meeting for pulling together scientists and patient advocates to talk about progress in the field.

CIRM has transformed our booth into a mini recording studio to film interviews with advocates and scientists at the meeting. They talk about the importance of advocates spreading the word, what they hope to learn from the meeting and what they think all people should know about the field. Here's the first batch of videos:

Jonathan Thomas, Chair of the CIRM governing board: What do you want all people at this meeting to know about CIRM?

I don't think there's a real comprehensive feel for the fact that we are engaged in research going after 26 different diseases.

Keri Kimler, Vice President for Texans for Stem Cell Research: What is the reception to your message about the power of stem cell research in Texas?

There's a lot of misconception. I think that we do everything we can to educate on the true purpose of the research and that's to find solutions to unmet needs and to find cures and to find new treatments and I think that that usually works very well.

Roman Reed, Roman Reed Spinal Cord Injury Research Act: Is there something all advocates should learn and take home from the meeting?

It's incumbent on all of us to get the message out there because when you really know about stem cell research you know it's the right thing to do. What's wrong with trying to help the suffering?

Laurel Barchas, PhD candidate at UC Berkeley: Is there a point about stem cell research that you think all people should take away from this meeting?

What's striking about this conference is that I've met people who are working in law, working to educate people, working to educate patients, patient advocates. All of these people are coming together with the common goal of advancing stem cell research. No matter what you are interested in you can use your talents to push this research forward.

Don Reed, Vice President for the Americans for Cures Foundation: Is there a message that all patient advocates should go home and tell their friends and family members?

Get involved. There's so many opportunities for patient advocates to get involved. Everybody knows somebody with a disease or disability for whom the doctors have said there's no chance, there's no hope.

Judy Roberson, past president of the Huntington's Disease Society of America: Is there some important role you think advocates play at this meeting?

I feel like patient advocates get a lot from listening to the hopeful messages and I think they get encouraged by hearing our personal stories about how Huntington's disease as effected my family and that we are very hopeful about stem cell research.

Stem Cell Awareness Day October 5, 2011

2011-09-29T15:48:00.000-07:00

Stay tuned for a Stem Cell Awareness Day event near you. October 5 will bring stem cell lectures, tours and symposia to nearly 40 locations around the world. So far, there are events in six countries, five U.S. states and at least 25 locations in California, and more are being added every day. You can see a list of events on the website.

In addition to opportunities for the public to learn about stem cell research, CIRM grantees and staff are going into more than 50 high schools to talk about the field with high school students.

CIRM chair Jonathan Thomas is kicking off the event on October 4 from the World Stem Cell Summit in Pasadena where he's hosting a reception for patient advocates. Throughout the meeting we will be posting to this blog short video interviews with patient advocates talking about their hopes for stem cell research. Watch for those starting next week.

If people are interested in hosting an event contact Chris Stiehl at chris@stiehlworks.com.

A.A.

Rolling back the clock on muscle disease, aging

2011-09-28T09:26:00.000-07:00

Last week CIRM grantees at University of California Berkeley published a follow-up to some of my favorite stem cell research. I'm speaking personally here as a runner who is getting older and would like to turn my race recovery back to what it was in my youth.

Irina Conboy started investigating the slow response of aging muscle stem cells as a postdoctoral fellow in the lab of Thomas Rando at Stanford University (I've written about that work here). What they found is that older muscles in mice don't respond very effectively to muscle damage. But, and this is a big but, if those older mice have younger blood, the muscle stem cells work just fine. Strange, but true.

Since that discovery, Conboy and her lab at Berkeley has been piecing together the story of how and why the younger blood refreshes those old and tired muscle stem cells. In their latest work, which was published in the journal Chemistry & Biology, they show a way using a short-term dose of chemicals to roll back the clock on mature muscle and return it to an earlier state.

A press release from UC Berkeley says:

Building new muscle to replace old or damaged tissue is the routine job of muscle stem cells, or satellite cells. Stationed along the perimeter of adult muscle tissue, they wait for a signal to grow, divide and fuse into new muscle fibers when there’s damage to repair.

But that repair process gets worn out in people with Duchenne muscular dystrophy, a genetic condition in which muscles degenerate because of a defective structural protein and subsequent exhaustion of muscle stem cells. Muscle repair also becomes incapacitated with advancing age.

The group hopes that by turning back the clock, they can return the muscle to a state where it is better able to repair damage. The press release goes on to say:

The researchers say the next steps include testing the process on human muscle tissue and screening for other molecular compounds that could help de-differentiate mature tissue.

“This approach won’t work for all degenerative diseases,” said Conboy. “It might work for some diseases or conditions where we can start with differentiated tissue, such as neurons or liver cells. But patients with type I diabetes, for instance, lack the pancreatic beta-islet cells to produce insulin, so there is no functional differentiated tissue to start with. Our approach is not a replacement for pluripotent cells, but it’s an additional tool in the arsenal of stem cell therapies.”

The group is a long way from marketing the next race recovery beverage. They still have to show that the technique works in human muscle and that those more youthful cells are better able to repair damage.

CIRM Funding: Irina Conboy (RN1-00532-1)
Chemistry & Biology, September 23, 2011

A.A.

San Diego stem cell community gets a boost from CIRM

2011-09-27T15:03:00.000-07:00

The North County Times in had a nice story today about the effect of CIRM funding in the San Diego area. Bradley Fikes wrote:

In San Diego County, one of the country's top three centers of biomedicine, researchers say CIRM has greatly boosted stem cell science's profile and magnitude. That commitment is producing advances that will translate into patient health and an economic boost for the local life sciences industry, they say.

It goes on to discuss the new Sanford Consortium building that will open next month. The building received $43 million from CIRM, which the consortium used to leverage additional money to building the $115 million project that pulls together giants of the stem cell field from UCSD, Scripps Research Institute, the Salk Institute for Biological Studies, and the Sanford-Burnham Medical Research Institute. In addition to pulling great minds into one space, the building will contain research facilities that can be shared by member institutions.

As with all of the CIRM-funded buildings. The goal isn't just to build fancy space. The goal is to speed research by pooling ideas, encouraging collaboration, and providing much needed equipment in convenient settings to speed research along.

The story goes on to say:

Over at the Salk Institute, veteran researcher Inder Verma says the state program catalyzed the institute's involvement with stem cell research. The program paid for a shared laboratory at Salk devoted to stem cell technology. This "stem cell core facility" provides training and equipment for scientists interested in working with stem cells.

The core facility was especially important for those workingwith human embryonic stem cells, because of federal restrictions imposed by President Bush in 2001 on the use of its money for that research, Verma said. President Barack Obama relaxed those restrictions after taking office in 2009. The facility also works with artificial embryonic stem cells called IPS, or induced pluripotent stem cells, which are typically grown from skin cells called fibroblasts.

"Many people at the Salk wanted to work in this area, but they didn't know where to start, because they didn't have access to these cells, they didn't have access to the technology," Verma said. "But once we had a core facility, suddenly, a large number of labs, 16 to 17, began to do work in the area of regenerative medicine. My lab had almost no one working on stem cells, and now, there are six to eight people working on stem cells."

San Diego is one of three major research centers in California where stem cell companies and academic labs have flourished. The other two are in Los Angeles and San Francisco. This interactive map shows where CIRM's funding has gone.

A.A.

Progress in stem cell therapy for HIV/AIDS

2011-09-26T15:39:00.000-07:00

Last week the company Sangamo Biosciences announced good results from their HIV/AIDS trial in which they genetically altered patients' own T-cells. CIRM is following this trial closely, since it's the precursor to one being developed by a team of CIRM-funded researchers led by John Zaia at City of Hope that includes Sangamo.

According to Discover Magazine, the company reported last week:

The goal was to see if receiving these altered cells would let patients go off their anti-retroviral drugs. The results, reported at a recent conference in Chicago, were mixed—the cells didn’t always survive long in the fifteen people enrolled. But two patients saw their HIV levels drop 10-fold, and one patient who stopped his anti-retrovirals first saw a spike in virus levels but then had them decline to undetectable levels.

The work funded by CIRM is a next generation version of this trial. In both cases, Sangamo's technology is used to snip the DNA of cells taken from a patient's bone marrow. Those snips introduce a mutation in a gene called CCR5, which makes the protein that the HIV virus uses to enter a cell. No CCR5 gene means HIV can't infect the cells.

Doctors then reintroduce those cells into the patient. The idea is that the patient will then be resistant to the HIV in their bloodstream and eventually can go off drugs. In the recently reported study, the team altered the adult T-cells, which would supply a finite number of resistant T cells. The CIRM study will be altering the blood-forming stem cells, which give rise to T-cells, in hopes of creating a more permanent supply of HIV-resistant T-cells.

This video gives more information about the goal of the CIRM-funded team:

A.A.

More stem cell firsts -- spinal cord injury and blindness

2011-09-22T20:24:00.000-07:00

Tuesday was a very proud day here at CIRM headquarters. We were able to announce the enrollment of the first patient in a clinical trial funded, in part, by the agency. It was also a bit of a somber day as Paul Knoepfler pointed out in his blog yesterday. It meant the patient had recently undergone a life-changing tragedy that landed them in need of the hope the follow-on trials to this safety study might provide.

This morning's news feed brought a similar double-edged milestone. Stem Cells Inc, the Newark California-based biotech firm, announced that the day before their research team had injected adult neural stem cells into a spinal cord injury patient for the first time. The stem cells were administered at Balgrist University Hospital of the University of Zurich to a 23-year old German man who had suffered a spinal cord injury in an auto accident in April and was completely paralyzed below the waist.

A press release from the company posted on Yahoo has a quote from the patient that vividly points out the double-edged nature of this milestone to him:

"This terrible injury crossed out almost all my life plans, and has led me to an unexpected path. Participating in this clinical trial not only gives me a sense of hope, but it also helps move this important research forward."

There was another strong linkage between these two milestones. One of the lead surgeons at the Zurich hospital was Raphael Guzman who has a visiting appointment there and is on faculty at Stanford, where he is a colleague of Gary Steinberg who transplanted the cells in the CIRM-funded trial at Santa Clara Valley Medical Center.

Today's news feed brought a third milestone to our field. Advanced Cell Technology (ACT) announced that they had been given approval to begin the first clinical trial of cells derived from embryonic stem cells in Europe. They will be testing cells for a form blindness that strikes children called Stargardt's disease. Clearance to begin the trial came from the United Kingdom Medicines and Healthcare Products Regulatory Agency.

ACT launched a similar trial in the US in November 2010 and a second trial in January, this one for macular degeneration, the leading cause of blindness in the elderly. This summer the company announced the first patients were enrolled in each trial at UCLA in July.

Robert Lanza, chief scientific officer at ACT told a news organization in the UK in this morning's coverage:

"We're very pleased with the results so far. We're in the process of scheduling the next two patients for each of the two (US) trials."

We are keeping our fingers crossed that this early track record for safety holds.

DG

First patient enrolls in a clinical trial funded by CIRM

2011-09-20T13:08:00.000-07:00

Today is a landmark day for CIRM: We announced that the first patient had been enrolled in a clinical trial based on stem cell agency funding. You can read our press release here.

The patient was part of Menlo Park-based Geron's phase I trial for spinal cord injury, which was awarded $25 million from CIRM in May. Stanford neurosurgeon Gary Steinberg, MD, PhD, implanted the cells Sept. 17 at Rehabilitation Trauma Center at Santa Clara Valley Medical Center.

Stanford had this to say about the trial:

Researchers at Geron collaborated with Hans Keirstead, PhD, and his laboratory team at UC-Irvine to develop a way to coax human embryonic stem cells to become a mixture of cells that include oligodendrocyte precursors. Oligodendrocytes are cells in the brain and the central nervous system that wrap nerve cells with an insulating material called myelin. This myelin sheath is necessary for the transmission of the electric signals along the spinal cord that trigger muscles to move, and relay our sense of touch and temperature. Damage to this sheath caused by trauma is a common cause of paralysis.

To be eligible for the trial, patients must have recent (within 14 days of injury) non-penetrating damage to a specific region of their thoracic spine — an area roughly from the top of the shoulder blades to the bottom of the rib cage. The damage must cause complete paraplegia, meaning that they have normal sensation or movement to the level of the hands, but not from the trunk to the toes.

During the procedure, Steinberg applied about 2 million of the special cells, called GRNOPC1, directly into the injured area of the patient’s spinal cord.

“We are quite pleased that the surgery was completed successfully and the patient is doing well,” said Steinberg.

When the CIRM governing board voted to fund the Geron trial, spinal cord injury advocate Roman Reed wrote a guest blog entry in which he said:

In a truly historic partnership for stem cell research and cure, state funding from what has been called “Roman's Law” gave Hans Keirstead the seed money to achieve empirical evidence and proof of principle. Hans then sold his pioneering technique to Geron, and advanced biotechnology farther by founding California Stem Cell with the proceeds.

With admirable courage and determination, Geron pushed this science all the way to FDA approval to become the world's first embryonic stem cell derived human clinical trial.

Now our beloved state agency, the California Institute for Regenerative Medicine will provide funding to bring about a full and complete Human Clinical Trial!!

The Keirstead/Geron/CIRM Trials advances the entire field of stem cell research.

Today's announcement marks a milestone that is a critical step toward making safe and effective stem cell-based therapies available to patients.

A.A.

Meeting of California's stem cell minds

2011-09-19T13:58:00.000-07:00

Last week CIRM held our almost-yearly grantee meeting, which brought together our grantees from across California plus some international collaborators and world-renowned stem cell leaders who gave some riveting talks.

CIRM grantee Paul Knoepfler from UC Davis was blogging from the meeting. He had this to say:

Earlier I threw out there the idea that many different interested parties should come together to advance science. Something I called “big tent science” and “big tent team science”.

I think CIRM is an outstanding example of this idea in action and I could see that in evidence today at the CIRM Grantee Meeting here in San Francisco. It’s very inspirational.

He went on to share this from a talk by Craig Ventor:

The meeting was kicked off with a talk by Craig Venter, the amazing scientist who has pushed research forward in so many ways including sequencing the human genome and making the first synthetic life form.

Dr. Venter, who has been involved in some of the most cutting-edge, exciting science in the last century as well as founding or being involved in many scientific organizations, said this about CIRM:

"This is the greatest scientific organization founded in our era."

Being there what stood out was the wide range of diseases being studied by our grantees, all with the eventual hope of finding therapies. It's a real thrill to see signs of hope for the wonderful patient advocates I've gotten to know through CIRM, and for my friends and family, all of whom stand to benefit from this work.

We'll be posting more about the meeting, including videos of two talks (including Ventor's) and of a pre-meeting target product profile workshop, and a video montage of our grantees talking about their work.

A.A.

UCSF stem cell building: generating therapies and making news

2011-09-14T08:23:00.000-07:00

The new UCSF stem cell building has made the news again. The September 19 issue of The New Yorker, architecture critic Paul Goldberger features UCSF’s Ray and Dagmar Dolby Regeneration Medicine as one of three new science buildings in the United States “crafted with the specific intention of fostering interaction and connections, as a means of generating ideas.”

A press release from UCSF says:

Constructed on what Goldberger called an “eye-poppingly impossible site,” the building is home to some 300 scientists studying the earliest stages of cell and tissue development, with the goal of understanding and developing cell-based treatment strategies for such diseases as heart disease, diabetes, epilepsy, multiple sclerosis, Parkinson’s disease, Lou Gehrig’s disease, spinal cord injury and cancer.

This is one of the buildings CIRM partially funded back in 2008, when the agency realized that a critical component of generating new therapies was providing scientists with a place to work. CIRM's investment of $271 million leveraged $560 million from private donors and $322 million in commitments from the institutions themselves. UCSF has this to say about funding for the building:

The $123 million building was paid for with state and private funds. In 2006, Ray and Dagmar Dolby contributed $16 million to launch the university’s fundraising campaign for the facility. In 2007, UCSF received a highly competitive $34.9 million grant from California Institute for Regenerative Medicine (CIRM). In 2008, UCSF received a $25 million grant from The Eli and Edythe Broad Foundation. Last winter, UCSF received an additional $20 million donation from the Dolbys. The university has $12 million left to raise.

When Eli and Edythe Broad made their donation to UCSF CIRM made this video about our hopes for the stem cell buildings:

A.A.

Alzheimer's leader discusses stem cell progress

2011-09-13T13:37:00.000-07:00

Tom Vasich at the University of California Irvine did a Q&A with CIRM grantee Frank LaFerla in advance of the September 30 Southern California Alzheimer’s Disease Research Conference. La Ferla and his colleagues have been working on stem cell-based therapies for Alzheimer's disease.

In a question about the public health impact of Alzheimer's disease LaFerla said:

It’ll be enormous, especially locally. California has the nation’s largest baby boom population; Orange County by itself ranks fifth. Alzheimer’s is going to hit us hard, because age is the most significant risk factor for the disease. One of every 20 people over 65 will be affected by dementia, and eventually half of those over 85 will suffer from Alzheimer’s. This is going to put an amazing strain on our healthcare system and on families.

He went on to talk about his own research, funded by CIRM:

We’ve had a lot of success with animal models showing that neural stem cells can reverse Alzheimer’s-like cognitive deficits. We’ve progressed to creating a population of human neural stem cells that will be the basis of clinical trials on patients. We’re still in the early stages, and we’re fortunate to have received a grant from the California Institute for Regenerative Medicine that is supporting our work.

We had the pleasure of talking to LaFerla about this week a few years ago. In this video, he describes the work and the importance of finding a therapy for the disease.

A.A.

Stem cells from rhino skin

2011-09-09T15:11:00.000-07:00

Northern White Rhinoceros; Photo credit: San Diego Zoo

What are those rhinos doing in a stem cell blog? Researchers at Scripps Research Institute have converted skin cells from those rhinos (or their San Diego zoo-mates) into reprogrammed stem cells. The team also created stem cells out of skin samples from a primate called a drill.

Both projects came out of conversation between Oliver Ryder, the director of genetics at the San Diego Zoo Institute for Conservation Research, and Jeanne Loring, professor of developmental neurobiology at Scripps Research and CIRM grantee. Ryder’s team had already established the Frozen Zoo, a bank of skin cells and other materials from more than 800 species and wondered if the thousands of samples they had amassed might be used as starting points.

The group, which includes an intern from the CIRM Bridges to Stem Cell Research program, published their work in the September 4, 2011 advanced online edition of Nature Methods. According to a Scripps press release, the work has the potential of preserving and even strengthening populations of endangered animals.

One of the greatest concerns with small populations such as the northern white rhinos is that even if they did reproduce, which hasn’t happened in many years, their genetic diversity is inevitably and dangerously low, and such inbreeding leads to unhealthy animals.

But researchers are moving toward inducing stem cells to differentiate into sperm or egg cells. With that accomplished, one possibility is that scientists could take skin cells in the Frozen Zoo from long dead animals, induce pluripotency, trigger differentiation into sperm cells, and then combine these with a living animal’s eggs through in vitro fertilization. Otherwise-lost genetic diversity would then be reintroduced into the population, making it healthier, larger, and more robust.

Or, both eggs and sperm might be produced from the stem cells, with the resulting embryos implanted in live animals, a process that current research suggests could be much more reliable than existing cloning techniques.

Scientists are already exploring the possibility of producing sperm and eggs from stem cells as a potential solution to human infertility issues. Loring hopes that some of these groups might consider initial technique development using endangered species stem cells. “I think that work would be a lot easier ethically with endangered species than with humans,” she said, “so I suspect some people working in this area would love to have our cells for experiments.”

The press release goes on to quote Ryder:

“The best way to manage extinctions is to preserve species and their habitats, but that’s not working all the time.” The rhinos are a perfect example, he said, because there are so few. “Stem cell technology provides some level of hope that they won’t have to become extinct even though they’ve been completely eliminated from their habitats. I think that if humankind wants to save this species, we’re going to have to develop new methodologies.”

CIRM funding: Susanne Montague (TB1-01186)

- A. A.

Guest blogger Alan Trounson — August’s stem cell research highlights

2011-09-01T08:30:00.000-07:00

Each month CIRM President Alan Trounson gives his perspective on recently published papers he thinks will be valuable in moving the field of stem cell research forward. This month’s report, along with an archive of past reports, is available on the CIRM website.

This month produced several papers that address fundamental issues in the field of stem cell research and provided us with some rebuttal points for one-liners tossed at us by some of our critics. If you have followed the field you’ve heard detractors of embryonic stem cells say: “why are we wasting our time on a cell type that causes tumors.” That is because in their most primitive pluripotent state embryonic stem cells form a type of tumor called a teratoma. While no one has ever planned to place a still-pluripotent embryonic stem cell in a patient—the plan has always been to mature them into tissue-specific cells first—the criticism has remained. Now, a team at Stanford has shown a way of completely purifying those progenitor cells and removing all the pluripotent cells capable of forming a tumor. (We blogged about that work here.)

Our critics also state that embryonic stem cells are by nature “anti-life” because a very early stage embryo is destroyed isolating them. But now a Japanese team has succeeded in reliably and efficiently producing viable sperm from embryonic stem cells. The follow-on research to this project could go a long way to reducing infertility around the globe. And that is certainly a pro-life outcome.

Finally a series of articles dealt with a very real and looming issue for the field. What is the role for sham surgery, mimicking the placement of cells, in controlled clinical trials for cell-based therapies. This has become a particularly contentious issue in Parkinson’s disease where there is shown to be a physiologic reason for a strong placebo effect. If you are interested in this question I encourage you to read the three pieces cited in my literature summary this month.

Hope vs. hype in stem cell research

2011-08-30T13:19:00.000-07:00

A few weeks ago CIRM grantee at UC Davis Paul Knoepfler wrote a blog entry distinguishing hype from hope in the stem cell research field. This is no small task. The hype in this field is incredible (as evidence, see all too many headlines on the topic). But then, so is the hope. CIRM was voted into existence by the 59% of Californians who had high hopes for therapies coming out of stem cell research.

When I talk to patient advocates who come to our board meetings, or who speak at our spotlights on disease or who we interview for our video series they are filled with hope for the field (see Roman Reed, for example, who is filled with hope). What's hard in writing or speaking about stem cell research is describing that hope without veering into hype. Those new therapies will come — but they'll take a while. Anyone who says differently is on the hype side of the equation.

My personal favorite of Knoepfler's Hope vs Hype statements is this one:

Many stem cell therapies that really work are available now. Verdict = HYPE

Unless you are talking about bone marrow transplants, which are a form of stem cell transplant and have a long history of treating a wide range of blood diseases, other so-called "stem cell therapies" are hype. No other type of stem cell has gone through all three phases of clinical trials to prove that those approaches are safe and effective. Several cell types — adult and embryonic — are in clinical trials right now, and some portion of those will likely end up being effective. But the majority of those early clinical trials that you read about will likely need refining and rethinking before they eventually work.

Knoepfler wrote his blog entry right around the time that Tim Caulfield wrote a piece for the Canadian journal The Walrus about a talk he gave deriding stem cell tourism. Caulfield is Canada Research Chair in health law and policy at the University of Alberta. Turns out, you shouldn't insult stem cell tourism — in which people travel to foreign countries where therapies aren't well regulated — while in front of a room full of people who run those clinics. Ooops.

He relates stem cell tourism to former heath claims for magnetism and radioactivity. He says:

Research on magnetism resulted in the sale of products promising magical restorative properties, curing everything from gout to constipation to paralysis. According to one advertisement from the late nineteenth century, “There need not be a sick person in America… if our Magneto-Conservative Underwear would become a part of the wardrobe of every lady and gentleman, as also of infants and children.” More dangerous was the excitement over atomic physics in the early 1900s. The work of scientists such as Marie Curie in the field of radiology garnered considerable public interest, which led to an array of radioactive products, including skin creams, toothpaste, bath salts, and pills.

Skin creams? That sound familiar to anyone following the stem cell field today? Obviously, radioactivity has turned out to be extremely useful as a form of cancer therapy, so there was some real hope in that hype. The trouble is telling the difference, and explaining that difference to people who might be swayed to hope when presented with hype.

Here's something to be hopeful about: 44 CIRM research projects are in various stages of making their way to the clinic. Many of these are in cancer, heart disease, and other diseases that directly affect my family members. That gives me hope.

A.A.

Progress toward stem cell clinical trials?

2011-08-26T14:47:00.000-07:00

The CIRM governing board meeting yesterday, held on the Stanford campus, included a number of important agenda items — planning awards worth $1.8 million and changes to the grants review process to name a few — and one seeming sleeper item titled "Presentation and discussion of CIRM Translational Grant Portfolio."

Yawn, right? But that's the item that generated the most excitement among board members, particularly the patient advocate members who are often asked to talk about progress CIRM is making in generating new therapies in their disease areas.

Many who read a major newspaper in California have probably read assertions about CIRM's apparent lack of progress. No new therapies in five years of funding? Must be a failure! (This, despite the twelve or more years it generally takes to go from a good idea in the lab to a new therapy in the clinic.)

The grant portfolio presentation by Patricia Olson, executive director of scientific activities, and Ellen Feigal, VP of research and development, should answer those complaints. The document was attached to the agenda and is available here. It looks about as dull as it sounds, and in its current state has more acronyms than complete words. However, the message is an exciting one: CIRM has 44 awards that are all in the late stages of therapy development, many with the goal of beginning clinical trials in the next few years. These include teams working on cancer, blindness, spinal cord injury, osteoarthritis, diabetes, and neurodegenerative disorders like Parkinson's disease, Alzheimer's disease and Huntington's disease.

We'll be putting this information online in a more digestible form over the next few weeks.

In addition to support from board members, the presentation prompted a humorous plea from new board chair Jonathan Thomas to members of the press to please, next time, look at this analysis before writing that we haven't accomplished much. All that research closing in on clinical trials likely wouldn't have occurred without us. That's pretty phenomenal.

We've written previously about the reasons for funding the full pipeline of research (Where are the cures?). Out of hundreds of basic science projects only a few even get to clinical trial, and of all clinical trials only a small number result in a new therapy. If we do want to see new therapies one day (and we do) then we need a lot of good ideas that will feed into these translational awards and eventual come out the end of the research pipeline as new therapies. With these 44 awards we should be seeing a number of new clinical trials over the next few years, and one day some of those are going to be therapies in a clinic near you.

A.A.

Guest blogger Alan Trounson: What A Mouse’s Toe Tells Us about CIRM’s Investment

2011-08-25T15:02:00.000-07:00

Guest blogger Alan Trounson is President of CIRM

Yesterday, my colleague Uta Grieshammer used this space to describe a Nature paper out of Irv Weissman’s Stanford lab that sought to pin down which cells are responsible for the regrowth of the tip of a mouse’s toe after amputation.

Salamanders and many lower organisms have the ability to regenerate whole limbs and most of their organs. However, while mice and men have the capacity to regrow parts of certain organs, notably the liver, they have lost the ability to replace any part of our limbs other than the very tip of digits—fingers and toes.

How does this relate to CIRM’s research investments? Some critics of our model, notably one writer at the New York Times, have suggested that we would have better spent our taxpayer investment entirely trying to figure out how salamanders accomplish their more robust regeneration. Specifically, the recommendation was that CIRM should be directing researchers to investigate the salamander cells responsible for this feat – called the blastema.

A long-held theory suggested that in salamanders, adult cells at the site of injury can be dedifferentiated into a stem-like state called a blastema that can then go on to produce all the cell types—bones, skin, tendon, vessels and nerves—needed to regrow the digit tip. The Stanford work very clearly showed no evidence of such a blastema cell in mice. They labeled the adult cells of each tissue type with a different color florescent marker and after regrowth they saw very clear demarcations of color between the various tissue types. The skin cells formed skin and the bone cells formed bone.

CIRM funded this work in keeping with our philosophy of funding the full spectrum of stem cell research, across all cell types, and in basic research funding work that looks at all aspects of stem cell growth and maturation. By funding stem cell research broadly, we believe we have had more successes than if we had concentrated our funding on any one aspect of stem cell research.

Of salamanders, mice and men - digit regeneration mechanisms revealed

2011-08-24T10:07:00.000-07:00

Regenerated mouse digit tip/Yuval Rinkevich

Guest blogger Uta Grieshammer is a science officer at CIRM

A form of regeneration that has captured the imagination of scientists and the general public for many decades occurs in certain salamanders, as they have the remarkable ability to regrow a severed leg. Leg regeneration is unusual not only because it is so rare among vertebrates, but also because the underlying mechanism is thought to be quite different from that operating during the regeneration of organs in mammals.

Although mammalian legs do not regenerate, the very tips of our fingers and toes, and those of mice, do sometimes regrow. A new study published August 24 in Nature from Irv Weissman’s lab at Stanford University, and partially funded by CIRM, now comes to the surprising conclusion that the mechanism at work during mouse digit tip regeneration more resembles that of our other organs rather than the way that salamanders’ legs have been thought to regrow.

Although it may not be obvious, many of the organs in a healthy person regenerate themselves throughout life, some more than others. Our whole blood forming system and our gut, for instance, turn over relatively rapidly, whereas only about half of our heart cells are replaced in our entire life. Some organs, such as our skin, muscles, and bones, also have a reasonable capacity for repair after injury, if the damage was relatively small, while much of our liver will be faithfully replaced after a large portion has been removed. Other organs, though, replace cells lost to insult or disease only poorly or not at all, such as the heart following a heart attack. The hope is, if we figure out how the regeneration superstars of our body, or those of salamanders, accomplish their remarkable feats, we can use that knowledge to coax their less talented brethren into action.

Scientists have three basic models for how regeneration occurs: 1) tissue-specific stem cells within the organ divide and mature into the additional tissue, 2) mature cells divide to produce more of themselves without contributing to other cell types, or 3) mature cells lose their specificity, become more like embryonic cells and form a blastema with the ability to divide and form the original cell type and also other cell types in the regenerating tissue.

Weissman’s work with postdoctoral scholar Yuval Rinkevich, who was first author on the paper, shows that during digit regeneration in mice, the third model is not the right one. Remaining skin cells only make new skin cells, bone cells only make new bone. This comes a bit as a surprise, as this appears to be very different from the blastema mechanism thought to be used by salamanders to regrow their limbs. However, recent experiments from Elly Tanaka’s group in Dresden have challenged that long held model, showing that blastema cells in regrowing salamander legs do not typically adopt fates different from those of the cells they’re derived from. These studies then suggest that regeneration of limbs and digits in salamanders and mice, respectively, does occur through related mechanisms, just not the one originally thought. In both cases, repopulating cells do not switch cell fate, but whether regenerated digit or limb cells are derived from tissue-specific stem cells or from mature cells remains an open question for both species, although the Weissman paper makes a cogent argument that their data are consistent with the stem cell model, at least for some of the cell types involved in mouse digit regeneration.

Concerted efforts by scientists studying animals such as salamanders and mice will likely lead to an ever more accurate picture of limb and digit regeneration, thereby laying the groundwork for translating these findings to human cells, and eventually to human treatments.

CIRM funding: Irv Weissman (RC1-00354)
Nature, August 24, 2011

New journal focuses on developing stem cell therapies

2011-08-22T12:29:00.000-07:00

In March 2011 CIRM began working with AlphaMed press to develop a new peer-reviewed journal to publish research that is translating basic stem cell science into new therapies. The idea was simple. AlphaMed had been publishing the elite journal Stem Cells for 30 years and recognized that the time had come to form a new journal focusing on the next phase of the science. The phase where all that early science published in Stem Cells started turning into therapies. At the same time, CIRM leaders were realizing that the scientists they were funding didn't necessarily have an elite journal focused on their work.

Turns out great minds were thinking alike, and before long CIRM and AlphaMed press had plans in place for their new collaboration. At the time, CIRM President Alan Trouson said:

“Science moves forward through publications in outstanding, peer-reviewed journals,. This new publication will provide a venue for studies that move stem cell research closer toward clinical trials. In addition to publishing new discoveries that help all scientists in their goals the journal will also take the unusual step of publishing studies considered negative, with results that did not back up the original hypothesis or that did not show a new path to therapies, which will save other scientists the time of carrying out those experiments.”

CIRM is supporting the journal for the first three years, then the journal is expected to be self-funded.

We had a chance to meet with AlphaMed president and vice president Ann and Marty Murphy today to talk about how things are coming along. The first issue is due out in January and they already have a pipeline of outstanding papers. Scientists interested in publishing in the journal can get information about submissions on the website www.stemcellstm.com.

They've also put a few interesting videos on the site, including journal editor Anthony Atala's short speech introducing the rational for the new journal. In the video he says:

"The mission of the journal is to bring together the best scientific papers in the field that will chart the course for the future not only for our investigations but also for the benefit of our patients and their healthcare."

A.A.

GMP grade embryonic stem cell lines approved by NIH

2011-08-19T12:10:00.000-07:00

The NIH has approved four new human embryonic stem cell lines for federally funded research. The lines, from CIRM-funded BioTime, have one thing going for them that many other lines don't. They were developed in compliance with Good Manufacturing Practice requirements, which is a critical step for developing a transplantation therapy. The FDA will only allow clinical trials involving cells and materials that were developed according to GMP guidelines, which carefully control the quality and consistency of a product. Working with cells that are already GMP-compliant removes that time-consuming step from the process of submitting a new clinical trial to the FDA.

Medical News Today quotes BioTime President and CEO, Michael West:

"This approval is key to our strategy of making our bank of GMP-compliant hES cell lines the industry standard for the development of a wide array of new human therapeutic products. We believe our ESI hES cell lines are the best characterized and documented lines available today. Our clinical grade hES cell lines were derived using procedures and documentation that are in compliance with current Good Tissue Practices (cGTP) and cGMP, which we believe will facilitate the transition of therapeutic products derived by researchers from these cell lines from laboratory to clinical use. We're grateful the NIH has approved the use of ESI-014 and ESI-017 and we look forward to working with researchers to translate the science into commercially successful therapeutic products."

In December 2010 BioTime agreed to make research grade versions of their embryonic stem cell lines available to CIRM researchers. According to a BioTime press release those have been supplied to dozens of researchers throughout California.

A.A.

Stem cell therapy gives dog a new leash on life

2011-08-18T13:11:00.000-07:00

Here's a happy stem cell story for the dog days of summer: A veterinarian in Pennsylvania used an experimental stem cell therapy to help a dog regrow severely burned foot pats. The dog, named Bernie, had been left on a scorching rooftop for 10 hours.

According to the Reading Eagle:

When the dog was brought to the shelter, an examination found he also had burn marks on his spine and his nipples. Officials believe the dog received those burns by lying down on the hot roof, trying to take weight off his painful paws.

"I don't think I've seen anything that bad in 25 years," said Dr. Boyd Wagner, veterinarian and owner of the Wyomissing Animal Hospital. "They were severe, third-degree burns."

Wagner worked with California-based Celevet, which is developing stem cell therapies for horses and dogs. There's not much information available about the type of cells Wagner used -- "stem cells" is a pretty loose term -- or how they were used to repair the foot pads. According to the story it's also not yet clear whether the therapy worked.

Still, as a dog owner it's nice to read about stem cells -- whatever kind they used -- helping give Bernie a chance at a better life.

A.A.

Cells derived from embryonic stem cells, iPS cells appear immature

2011-08-17T11:38:00.000-07:00

A trend over the past few years has been comparing embryonic stem cells, adult stem cells and reprogrammed adult cells (also known as iPS cells) to each other and to other cell types. The goal is to understand what the cells are, exactly, and and how they differ from each other. Eventually this information could help researchers learn which type of cell will be most effective for developing therapies, understanding diseases or drug screening.

A group of CIRM grantees at UCLA has published the latest in the unfolding story of stem cell comparisons. In their case, they didn't compare the stem cells themselves. Instead, they matured embryonic stem cells and iPS cells into the cells that eventually form neurons, cells that eventually form skin, and cells that eventually form liver. These so-called progenitor cells also exist in adult humans, where they lurk in tissues waiting to be needed to repair damage.

The scientists compared the progenitor cells to each other and to equivalent cells taken from adult tissue as well as to developing tissues. What they found is that the progenitors for nerves, skin and liver that came from embryonic or iPS cells had a lot in common with each other and with developing tissues. However, they had much less in common with their counterparts taken from adult tissues.

A press release from UCLA quotes William Lowry, who was senior author on the paper, which appeared in Cell Research.

“What we found, looking at gene expression, was that the cells we derived were similar to cells found in early fetal development and were functionally much more immature than cells taken from human tissue. This finding may lead to exciting new ways to study early human development, but it also may present a challenge for transplantation, because the cells you end up with are not something that’s indicative of a cell you’d find in an adult or even in a newborn baby.”

The release goes on to quote first author Michaela Patterson:

“One important reason to do this is to ensure that the cells we are creating in the Petri dish and potentially using for transplantation are truly analogous to the cells originally found in humans,” said Michaela Patterson, first author of the study and a graduate student researcher. “Ideally, they should be a similar as possible.”

…

“The roles these cells play in the fetus and the adult are inherently different,” she said. “It may be that the progeny, if transplanted into a human, would mature to the same levels as those found in the adult liver. We don’t know.”

This is the first paper we've seen comparing progenitor cells to adult or developing tissues. As with all first steps, we'll likely see more papers over the next few years refining and expanding on this team's findings and clarifying what these findings mean in terms of transplantation.

CIRM Funding: William Lowry (RS1-00259-1), Michaela Patterson (T1-00005)
Cell Research, August 16, 2011

A.A.

Weeding out the tumor-forming cells from potential stem cell therapies

2011-08-15T10:53:00.000-07:00

CIRM grantees at Stanford University have removed some of the risk of therapies based on human embryonic stem cells or reprogrammed adult cells, known as iPS cells.

Both of these cells types are known as pluripotent, which means that the cells can go on to form all the mature cells of the human body. The problem is that those cells also form tumors called teratomas. In the process of developing new therapies, scientists first prod the stem cells into a more mature cell type, such as a neural progenitor for spinal cord injury, an insulin-producing pancreatic cell for diabetes or retinal cell for forms of blindness. Then, they go through a laborious process to show that no tumor-forming cells still remain in that batch of cells that they hope to use in therapies.

The new technique, published August 14 in Nature Biotechnology, provides a novel way of identifying cells that are potentially tumorigenic and removing them from a batch of cells. Krista Conger at Stanford wrote about this paper:

"The ability to do regenerative medicine requires the complete removal of tumor-forming cells from any culture that began with pluripotent cells," said Irving Weissman, MD, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine. "We've used a combination of antibodies to weed out the few undifferentiated cells that could be left in the 10 or 100 million differentiated cells that make up a therapeutic dose."

Weissman pointed out that the production of therapeutic cells from pluripotent stem cells for regenerative medicine was a major goal of Proposition 71, the ballot measure that established the California Institute for Regenerative Medicine to allocate $3 billion to advance stem cell science. CIRM funded this research.

…

"Commonly used differentiation protocols for embryonic stem and iPS cells often give rise to mixed cultures of cells," said research associate Micha Drukker, PhD. "Because even a single undifferentiated cell harbors the ability to become a teratoma, we sought to develop a way to remove these cells before transplantation."

If other research groups repeat these findings, the technique could reduce some of the risk of therapies based on pluripotent cells.

Nature Biotechnology, August 14, 2011

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High school students get stem cell experience in California labs

2011-08-12T09:27:00.000-07:00

UC Davis interns Rex Reyes, Jaskaran Dhillon, Thomas Gepts and Kalani Ratnasiri

Last week CIRM gathered together the Creativity Award interns to learn about their summer projects. These high school students came from UC Davis, UC San Francisco, UC Santa Barbara and Stanford to congregate at the Children's Hospital Oakland, home of CIRM board member Bert Lubin.

The goal of the awards was to give high school students experience in research labs, and to encourage those students to think broadly about science with the idea that novel therapies will come from creative thinking. The students all carried out additional projects in humanities or other areas of science. (We blogged about the program here.)

The students I met were incredible, and I'm apparently not the only person to think so. Charlie Casey at UC Davis did a story about the program quoting Jan Nolta, who directs the school's Institute for Regenerative Cures.

“These students truly exceeded our expectations,” said Jan Nolta, director of the UCD Institute for Regenerative Cures and a mentor for several of the students. “One of our other interns was so determined to learn about stem cell science that he traveled two hours from Vallejo and back each day to work in our Sacramento lab.

“All of these young people performed fabulously, and they represent a very bright future for science, particularly, I hope, in stem cell research.”

The Sacramento Bee wrote about the four UC Davis interns.

Program directors selected the students based on their award-winning presentations of biotechnology concepts on websites they designed for UCD's 2011 Teen Biotech Challenge.

The four took a course in the procedures and techniques of stem cell production with master's-degree students from California State University, Sacramento, and worked on individual projects with scientist mentors.

When I talked to Gerhard Bauer, who taught that master's-level course, he said the high school students held their own among those more senior students. It'll be a while before we know where these students end up. For now, it's exciting to see high school students—many from lower socioeconomic homes—get excited about college and about the potential for stem cell research.

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Heart cells divide again?

2011-08-10T14:30:00.000-07:00

One perplexing question in regenerative medicine is why the human heart muscle cells are unable to divide and multiply their numbers. If they could, maybe they'd be able to produce new heart cells to replace those lost after a heart attack. Newts and salamanders can do it, why can't we?

CIRM grantees at the University of California, Los Angeles have found one answer to the question, which could lead to a way of turning the cell's clock back to a time when they could still divide. Robb MacLellan, who was senior author on the work published in the Aug. 8 issue of the Journal of Cell Biology, said that the ability to divide is a trade off. A UCLA press release wrote:

MacLellan believes the reason adult human cardiac myocytes can’t [divide] is quite simple – when the myocytes are in a more primitive state, they are not as good at contracting, which is vital for proper heart function. Because humans are much larger than newts and salamanders, we needed more heart contraction to maintain optimum blood pressure and circulation.

MacLellan suggests that it might be possible to get the heart cells dividing again by blocking the proteins that are halting the cell cycle. The press release had this explanation:

When a heart attack occurs, oxygen is cut off to part of the heart, causing the cardiac myocytes to die and resulting in scar tissue. It’s easy to locate the damaged area of the heart, and if a way could be developed to reprogram a patient’s own myocytes, the protein manipulation system could be injected into the damaged area, reverting the myocytes to their primitive state and replacing the dead muscle with new, living muscle, MacLellan said.

“People have been talking about the regenerative potential of these lower organisms for a long time and why this does not occur in humans” MacLellan said. “This is the first paper that provided a rationale and mechanism for why this happens.”

…

“From my point of view, this is a potential mechanism to regenerate heart muscle without having to harvest or expand stem cells,” MacLellan said. “Each person would be their own source for cells for regeneration.”

MacLellan has two CIRM Basic Biology (Basic Biology I, Basic Biology III) awards to study human heart progenitor cells.

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Mountain climbing raises money for stem cell research, Parkinson's disease

2011-08-09T13:12:00.000-07:00

A group of Parkinson's disease patients and family members have hit on a new twist to athletic fundraisers. Forget the local charity 10K race — they are hiking 19,000 foot Mt. Kilamanjaro in Tanzania to raise money for The Scripps Research Institute's Center for Regenerative Medicine, headed by CIRM grantee Jeanne Loring.

Loring has CIRM grants to understand what makes a stem cell a stem cell, to define ways of purifying stem cells and to help prevent the immune system from rejecting transplanted stem cells. She is also part of a project to develop stem cell-based therapies for Parkinson's disease, which this trek will help fund.

A North County Times story describes the project like this:

The stem cells will be produced from human skin cells of patients, transformed into IPS cells, then grown into the proper kind of cells. In the case of Parkinson's patients, these will be dopamine-making neurons. If all goes well, these replacement cells will be transplanted into the patients, making the missing dopamine, and relieving or curing their symptoms.Because the transplants will be autologous, immune reaction is not expected to be a problem.

On August 4, Loring and other members of the research team discussed their research with the group, organized as Summit4StemCell. Those talks are available on the North County Times website.

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A fifth group turns skin to neurons, creating a model for Alzheimer's disease

2011-08-05T13:11:00.000-07:00

A few weeks ago, my colleague used this space to discuss the second and third papers showing teams had turned skin cells directly into neurons, noting that this replication of research results is essential to verifying the initial breakthrough while refining and improving it. She noted that only after much replication and refinement would she or anyone else want the resulting cells for therapy. Since then a fourth team reported another technique and now a fifth group is reporting the more likely short term benefit—a disease in a dish model for a neurodegenerative disease.

The first two papers came from work in the CIRM funded facility at Stanford University. The breakthrough paper in May from Marius Wernig reported a slow and inefficient process for using certain factors to directly reprogram skin cells into nerve cells without first taking them through an embryonic-like state. The follow-up paper in late July came from Stanford colleague Gerald Crabtree and showed marked improvement in efficiency and the nerve-like functioning of the cells. That same week at team from Milan reported another efficient system for creating nerve cells but this time directing them to become dopamine-producing cells like those lost in Parkinson's disease. And last week at team at the Gladstone Institutes in San Francisco, using another CIRM funded facility, reported yet another technic that also improved efficiency.

Now, a team at Columbia reported in today's issue of the journal Cell that they had developed a fifth way to accomplish this direct conversion of skin to nerve, and had done so with both skin from normal subjects and skin from patients with the inherited form of Alzheimer's disease. In both cases the cells matured and behaved like neurons, responding to neurotransmitters by letting ions like sodium and potassium cross the cell membrane. However, the cells derived form patients were also clearly abnormal. They had altered ability to process and transport the amyloid precursor protein (APP) and a resulting increase in production of amyloid beta, which has long been a suspect in the disease, but depending on what year you look at the literature, it is theorized to be a culprit or an artifact. This disease in a dish model may help to answer that question.

DG

NIH names friend of CIRM as head of its new stem cell center

2011-08-04T08:43:00.000-07:00

Francis Collins, director of the National Institutes of Health announced this morning that Mahendra Rao will become the first director of the new NIH Intramural Center for Regenerative Medicine (NIH-CRM). It will be good for CIRM to have someone in this new role who is very knowledgable about us and has been an active supporter of the agency. Rao has agreed to be a presenter in a Webinar we arranged for researchers to better understand the regulatory process, served as a speaker at a town forum when we have reached out to the public, and generally lent an ear when we have had questions about industry in the regenerative medicine space.

Rao is also on the research team for a CIRM grant at the Buck Institute, his part time academic appointment. His main day job for the past six years has been as the vice president of regenerative medicine at Life Technologies, based in Carlsbad, California.

An NIH press release quotes Collins as saying:

"Dr. Rao's varied experience makes him perfectly qualified to bring large groups together in order to move stem cell technologies through clinical trials and beyond to the clinic."

The release noted that the major goal for the new center is to build upon existing NIH investments, to advance translational studies and ultimately to get cell-based therapies into the treatments offered at the NIH Clinical Center.

Rao is internationally known in the field and has done extensive research with human embryonic stem cells as well as adult stem cells. He has done stints in academia, government and industry. His PhD training provided another bond to California; he studied developmental neurobiology at Cal Tech. Story Landis, chair of the NIH Stem Cell Task Force commented on his experience in the NIH release:

"He brings extensive experience with human stem cell to the position as well as considerable energy and focus on moving to clinical applications."

D.G.

High school students get creative in California stem cell labs

2011-08-02T11:10:00.000-07:00

Smarts, education and hard work will get you far, but the big leaps in science take something more -- creativity. That's the thinking behind an innovative CIRM-funded summer program that encourages the most creative high school students to spend time working in a stem cell lab.

The CIRM Creativity Awards recipients are meeting in Oakland today to share results of their internship programs. Each student combined stem cells and one other discipline -- engineering, chemistry, social sciences, ethics, music or other academic fields -- into a summer internship.

This year's pilot program sent high school students to work in labs at Stanford and at University of California campuses in San Francisco, Davis and Santa Barbara. One student from each school was nominated to give a short talk about their research during today's meeting.

CIRM has worked to create a pipeline of stem cell expertise in California by funding young faculty, graduate students, masters and undergraduate students, ensuring that California has the scientific talent to fill biotech jobs and create the next generation of stem cell therapies. This high school program reaches even further down that pipeline, making sure promising high school students get the experience they need to go to college and earn science degrees.

This program is CIRM's second to reach high school students. Last year we released a high school curriculum that teachers can download and use to teach students about stem cell research. Those modules are here.

CIRM President Alan Trounson has been especially supportive of this program. Trounson was among the first to succeed with in vitro fertilization and believes that innovation and creativity are key to developing new therapies. When CIRM first announced this program he said:

“These Creativity Awards encourage smart young people in California to bring fresh ideas into the stem cell research field,” said Alan Trounson, CIRM President. “We are not only supporting the next generation of stem cell scientists, we are promoting the kind of innovative thinking that leads to novel breakthroughs in science.“

We'll be releasing videos in the upcoming weeks of talks by these students and an overview of the program.

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Lung airway stem cells awry in cystic fibrosis

2011-07-29T13:28:00.000-07:00

Recent research from the University of Iowa suggests that people with cystic fibrosis have fewer of the stem cells that would normally repair the airway.

In most people, glands in the airway secrete bacteria-killing factors to help fight infection. These glands are also home to airway stem cells that rebuild the glands and keep them functioning normally. The Iowa team found that in people with CF, the airway stem cells had packed up and moved to the surface of airway rather than being nestled in the protective glands.

The team didn't find a clear cause and effect, but they suggest that with fewer airway stem cells, those glands are less able to repair themselves and secrete factors to help ward off infection. John Engelhardt, Roy J. Carver Chair in Molecular Medicine and professor and head of anatomy and cell biology who led the research, suggests that the next step might be to learn how to manipulate the environment, or stem cell niche, of those glands so that the stem cells will stay put and keep the glands functioning properly. Such a therapy could help prevent the infections that wreak such havoc on people with CF.

A University of Iowa press release quotes Engelhardt:

"This is the first demonstration that lung stem cell niches may be altered in CF." … "The future excitement of these findings relates to the potential of manipulating lung stem cells through neuropeptides or their inhibitors."

The work was published in the July 18 issue of July 18 issue of Journal of Clinical Investigation.

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Tracking stem cells using tricks learned in outer space

2011-07-28T08:20:00.000-07:00

Stem cell science is set to get a boost from an unlikely source: outer space. It turns out that techniques devised to help telescopes peer through the blur of the earth's atmosphere could help scientists peak more deeply into tissues. If the technique, called adaptive optics or AO, works it might prove useful for scientists hoping to track the whereabouts of transplanted stem cells.

A group of researchers at the University of California, Santa Cruz, including CIRM grantee Joel Kubby, have formed the W. M. Keck Center for Adaptive Optical Microscopy, which will apply AO techniques to microscopes built for peering deep into tissues.

A press release from UCSC describes the project:

Principal investigator Joel Kubby, an associate professor of electrical engineering in the Baskin School of Engineering at UCSC, has worked on adaptive optics (AO) systems for large telescopes as well as for biological imaging. In astronomy, AO systems correct the blurring of telescope images caused by turbulence in the Earth's atmosphere. In microscopy, blurring is caused by the flowing cytoplasm of living cells.

"We can get beautiful images of cells close to the surface of the tissue, but if you want to go deep you're out of luck because of the degradation of the image. That was the motivation for this project," said co-investigator William Sullivan, professor of molecular, cell, and developmental biology at UC Santa Cruz. "For cell biologists, anything that improves imaging is a big deal, and this has the potential to open up vast areas of cell biology that have been opaque to us."

In stem cell research, for example, an important bottleneck in efforts to develop stem cell therapies has been the inability to follow injected stem cells and monitor their fates below the surface of the tissue. AO microscopy could solve this problem, and the California Institute for Regenerative Medicine (CIRM) has provided support for the work at UCSC, including funding that led to the development of the team's first AO microscope.

Knowing where a stem cell goes once it has been transplanted is critical to developing new therapies. Unless they go to where the damage is and stay there, those cells won't hold any long-term therapeutic benefit. Tracking cells within tissues could point to better ways of transplanting the cells and, eventually, to more effective therapies.

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A history of the stem cell lawsuit & what it meant to California scientists

2011-07-27T10:16:00.000-07:00

Today U.S. District Judge Royce Lamberth dismissed a lawsuit that has been creating uncertainty for stem cell scientists for almost a year. The Washington Post quotes Lamberth's opinion:

“This Court, following the D.C. Circuit’s reasoning and conclusions, must find that defendants reasonably interpreted the Dickey-Wicker Amendment to permit funding for human embryonic stem cell research because such research is not ‘research in which a human embryo or embryos are destroyed,’ ” Lamberth wrote.

Here's some history on the lawsuit from this blog:

What the embryonic stem cell research ban means to California researchers (8/27/2010)
Government appeals stem cell ruling, claims harm to patients (8/31/2010)
The ups and downs of federal funding for stem cell research (9/9/2010)
Legal wrangling slows Stanford researcher's quest for a cure (9/15/2010)
U.S. Appeals Court decision--good news, but not the final word (4/29/2011)

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Discoverer of brain stem cells becomes president of ISSCR

2011-07-26T10:38:00.000-07:00

The North County Times had a good story yesterday about Fred Gage's new role as the president of the International Society for Stem Cell Research. Gage is a renowned stem cell scientists at The Salk Institute for Biological Studies, which also wrote about his new role.

Gage was the first to show that people do, in fact, produce new brain cells after birth. In work that is especially close to my heart, he also showed that mice that get (to quote the 1999 press release) "regular voluntary exercise on running wheels" also grow more brain cells than sedentary mice.

More recently, Gage has had CIRM funding to carry out studies modeling human neurological diseases in a lab dish as a way of understanding and treating those diseases. We've blogged about his work here and here.

As the new president of ISSCR, which represents about 4,000 stem cell scientists internationally, Gage said he hoped to advocate for stem cell science to the public and to politicians. He also hopes to advance ISSCR's mission of moving basic stem cell discoveries into clinical therapies. He told the North County Times:

"There's been a lot of fantastic basic research that has been done," Gage said. "We realize that part of our mission as a society is to translate these basic science into clinical applications. We call it bench to bedside. We're thinking about ways to do this most effectively."…

"You have to have the basic biologists helping in this, but we need the clinicians too, even though they don't have the (scientific) knowledge," Gage said. "We need to bring them up to speed. And underlying all this, we need to have a very effective fundraising effort for the society."

Gage talked to CIRM about how stem cells can be used to mimic disease in a lab dish:

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