Tuesday, April 22, 2014

Shape-Shifting Stem Cells Could Inform New Wave of Absorbent Technologies

A unique, shape-shifting property—previously only identified in man-made materials—has been discovered to also exist in stem cells.

In a study published on Sunday in the journal Nature Materials, scientists at the University of Cambridge, UK, describe a strange event that occurred when observing the physical changes that occur as stem cells grow and mature into the various cell types in the body.

Most materials in nature, when stretched or squeezed, will then revert back to their original shape. But a select few materials will do the opposite: once stretched or squeezed they maintain their new shape. These so-called “auxetic materials,” which can act as a kind of super-absorbent sponge, are of great interest to materials scientists and engineers looking to improve methods to create everything from soundproofing to bulletproof vests.

In this study, the research team—made up of biologists, engineers and physicists—were completely shocked when they saw stem cells exhibiting distinct auxetic properties as they began to transform into tissue-specific cells. As the study’s lead author Kevin Chalut noted in a recent news release:

“When the stem cell is in the process of transforming into a particular type of cell, its nucleus takes on an auxetic property, allowing it to ‘sponge up’ essential materials from its surroundings. This property has not, to my knowledge, been seen before at the cellular level—and is highly unusual in the natural world.”

Chalut and his colleagues were able to spot this unique property by treating the fluid that surrounds the cell’s nucleus, called the cytoplasm, with a particular type of dye. As the cell transformed and matured into a tissue-specific cell, the nucleus absorbed the colored dye. This was an indication that the nucleus itself was expanding—perhaps in order to absorb key molecules residing in the cytoplasm that are required for a transformation.

This research stands to not only improve our understanding of stem cells’ underlying molecular biology, but also to inform the related fields of engineering and materials science. It is a strong reminder of the importance of basic research; that even as the field of regenerative medicine moves forward into the clinic, it is still vital for organizations such as CIRM to support and foster this type of research.

As CIRM-grantee Irv Weissman stated in a recent video on the importance of basic research:

"This happens over and over again in basic research. If you keep your mind open you will begin to see things."

A biophysicist by training, Chalut agrees, stating that that his team’s discovery is just another indication of how much we still have to learn about nature:

“Despite great technological effort, auxetic materials are still rare and there is much to discover about them…. [But] studying how auxecity evolved in nature will guide research into new ways to produce auxetic materials, which might have many diverse applications in our everyday life.”

Anne Holden

Monday, April 21, 2014

Stanford Researchers Develop New Technique that can Map a Cell’s Genetic ‘Blueprint’

There are many different types of cells in the human body, but they all have something in common: housed within each is the complete set of genetic instructions, our genome, that give us life. It turns out that what makes cells different—what guides a blood cell to become a blood cell—depends on which parts of the genome are switched on, and which remain silent.

That much has become clear in recent years. But as far as the underlying molecular processes that guide these genetic ‘switches’? Scientists are still trying to figure out how it all works.

Luckily, a team of engineers at Stanford University made a significant break in the case: a way to map the growth of a single cell at the molecular level, gene by gene and day by day. The result: a procedure that effectively ‘reverse engineers’ a specific type of mature tissue from a single cell—knowledge that stands to improve scientists’ understanding of how cells transform from an all-purpose, stem cell-like state, into the various cell-types in the body.

The research team, led by Stephen Quake from the Stanford School of Engineering, focused on the types of lung cells that make up the alveoli, the small structures that serve as ‘docking stations’ for blood vessels to receive oxygen and expel carbon dioxide. In order to achieve their results, which were published in the April 13 issue of the journal Nature, the team required a few ingenious pieces of technology.

First, a specialized device, akin to a molecular ‘eye-dropper,’ that allows for collecting a single cell inside a chamber to study. And second, a way to detect the genes that were being switched on in that cell as it matured over time.

That specific set of tools, however, did not exist. So the research team built them. And in so doing, they were able to shed light on what had until now been a very nebulous process.

Using their newly developed tools, Quake and his team discovered that the two main types of alveolar cells, called (fittingly) alveolar type-1 and alveolar type -2, both derive from the same early-stage lung cell. This is despite significant physical differences and functions between the two types. The team’s technique also allowed them to capture cells at critical moments in time, for example as they transitioned from an early, stem cell-like state into a more mature alveolar-like cell.

Though pioneered in lung cells, this technology could be applied to a wide variety of cell types—and therein lies the rub. As Tushar Desai, the study’s co-author and an assistant professor at the Stanford University School of Medicine explained in a news release:

“This technique represents a quantum leap forward in our ability to apprehend the full diversity of cell types, including the rare ones that could have special functions. Because of a comprehensive molecular characterization of each [cell] type is achieved, a snapshot of the communication between individual cells will also emerge—and may suggest attractive therapeutic targets in disease.”

Indeed, this study highlights the important relationship between the fields of genomics and the stem cell research; a relationship that CIRM believes must be fostered, as evidenced by the creation of the new Center for Excellence in Stem Cell Genomics earlier this year. As CIRM President Alan Trounson stated in the January news release announcing the new Genetics Center:

“That deeper knowledge, that you can only get through a genomic analysis of the cells, will help us develop better ways of using these cells to come up with new treatments for deadly diseases.”
Anne Holden

Friday, April 18, 2014

Stem cell stories that caught our eye: therapeutic cloning, growing nerves and reprogramming cells.

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

A modest advance in therapeutic cloning. This week a Korean team announced that they had used the same techniques used by an Oregon team just about a year ago to create the first embryonic stem cell lines by a process known as Somatic Cell Nuclear Transfer (SCNT) that is commonly called therapeutic cloning. The process requires putting the nucleus of an adult cell into a donor egg and tricking the egg into thinking it was fertilized so that it begins to divide. The main advance in the current announcement deals with the age of the donor cells. The Oregon team took the nucleus from cells from a small skin sample of newborns, but the Korean team used much older donors, one as old as 75. Since our the genetic material in the nucleus of our cells is known to become less robust and amenable to change as we age, getting the procedure to work with older donors is important for true therapeutic cloning where the goal is creating stem cell lines that can give rise to repair tissues that genetically match the patient.

Much of the coverage was a bit overwrought about the degree of this advance and some of it predictably raised the specter of full human cloning, which no one envisions. Forbes did a nice piece putting the cloning issue in perspective and Reuters’ wire story used a good quote from Harvard’s George Daley placing the work in perspective with prior research. We wrote about some of the controversy created by the original Oregon cloning research last year.

Lab-grown esophagus long way from clinic. A paper in the journal Nature Communication about growing an esophagus in the lab for a rat patient got a good deal of pick up in the media this week—probably more than it deserved. This may have been in part because the main researcher was Paolo Machiarini who has received considerable press for his prior work creating replacement trachea for human patients. But being a simple airway, the trachea is considerably easier to mimic than the esophagus that has to deal with a regular barrage of food of many textures. Also the rat esophagus in this study is much smaller than a human replacement would need to be, and the report only involved three rats, so the entire study should be viewed as very preliminary. The Huffington Post did a better job than most outlets in putting the work in perspective.

Could Silly Putty be good for your brain? It is amazing how a reference to a toy from our childhood increases the press attention to some pretty serious science. We have often written about the importance of paying attention to the neighborhood a stem cell grows in if you want it to mature into the type of tissue you want. A team at the University of Michigan found that embryonic stem cells much more readily become the type of nerves that control our muscles if they are grown on threads from one of the key components of Silly Putty. Since maturing stem cells into specific tissues remains the end goal of much of our field, this is important work and was published in the prestigious journal Nature Materials. But it might not have seen the light of day in the popular press without that Silly Putty. Kudos to the writer at U of M. Red Orbit did one nice piece on the work and the site The Doctor Will See You Now did another.

Great update on reprogramming cells. For serious science wonks who want to catch up on some of the absolute latest science on cell reprogramming Nature posted a blog from a conference CIRM sponsored with the Keystone group just last week. It covers disease modeling, getting stem cells in a dish to mimic the older cells seen in diseases of aging, and many more topics.

Don Gibbons

Is the ability of European scientists to work with human embryonic stem cells being jeopardized by DIY (do it yourself) communication

Guest blogger Sergio Pistoi served with me on the Public Education Committee of the International Society for Stem Cell Research and in 1998 was a fellow in a science journalist fellowship program I directed at Harvard Med School. He writes for many major publications and consults with scientist on communicating their work. In the latter role he has found reason to disagree, in part, with a recent Nature editorial that lamented the European parliament system forcing a second debate on human embryonic stem cell research in less than a year.—Don Gibbons

In 2012, I attended a meeting on human embryonic stem cells (hESCs) at the EU parliament in Brussels. The room was packed with members of the parliament and other influential decision makers. Top experts came to present their (really) exciting results with hESCs in an understandable way. It was clearly a lobbying effort to support the funding of hESC studies, which was under ferocious discussion at the EU parliament (eventually, the parliament voted to continue funding under the Horizon2020 framework program).

The first speaker, a prominent stem cell expert, showed beautiful microphotographs of a blastocyst (the early-stage embryo that provides the original material for hESC lines) and asked the audience to reflect on whether it could be labeled as a "human life." That was fair and effective. People had an opportunity to look at the real, pin-point-size human cell-ball (a blastocyst contains only 200-300 cells) and make up their own mind without any bias. So far so good.

Unfortunately, seconds later the same speaker went on with elaborate scientific arguments to demonstrate that using those cell balls does not equal to a "destruction of human life". On a personal ground, I agreed with him. But as a communication professional, I started smelling an incoming disaster. And I didn’t have to wait for long.

A member of the European parliament from Slovakia, with whom I have had some small talk before, suddenly interrupted the speech. "How dare you to come here and tell us when human life begins?" he heckled. The guy was intending to provoke—he was a notorious opponent of using hESCs. But he was damn right. There little scientific ground in telling at which stage of development a human life begins; it's a matter of personal belief, not biology.

By uttering scientific statements on the topic, the speaker had exposed his flank to strong criticism. Worse, he was totally unprepared to face such reaction. As a result, he was grilled on the spot by the Slovakian, who had piles of EU documents supporting his own view and made an easy way into muting the hESC-supporting scientist. The organizer, a British MEP, was embarrassed.

I personally know most of the scientists that spoke that day: they are great researchers and honest, unassuming persons who are strongly engaged in society and dissemination. Nevertheless, I am pretty sure that some people in the audience were left thinking that those “experts” might be just a bunch of arrogant eggheads.

Such a pattern of good-intentioned-and-yet-abortive communication is common and may sound familiar to many readers. The Brussels communication screw-up was just one out of dozens that I have witnessed. And I am still counting.

The reason for such failures is often obvious to the trained eye: total lack of strategy. As it turned out, none of the speakers in Brussels had discussed a simple plan beforehand with their colleagues, the organizers, or a communication professional. Had the first speaker consulted a bona fide communicator, he would have been advised about the risk of being roasted. Just for starters.

It’s amazing how many good scientists overlook the importance of strategic communication. I could make a list of top researchers who think that they don't need to waste time and money on a communication plan, or believe that their DIY plan is perfect (which I find even more worrying). These people would call an expert with degrees to fix the air-conditioning of their labs, but will never bother to hire a professional to get some advice on communication. I know it sounds like the old, bleak squabble between journalists and scientists but, believe me, it isn’t. I was a researcher myself and, actually, there is no squabble. There are good scientists and good communicators and they should team up against the poor ones in each category.

Enter this week's Nature editorial about a new petition that aims to stop funding hESCs research in the EU. According to the EU rules, any petition signed by at least 1 million citizens automatically prompts a formal parliamentary hearing. This mechanism sounds like democratic heaven but, in fact, says Nature, it gives to a minority of people (1 million is 0,4% of the EU population) the power to endlessly restart the debate on topics that were already voted by the Parliament. The editorial states:
"When it comes to complex, highly emotional issues, passionate minority groups can easily and quickly drum up well-supported petitions in a way that scientists cannot," which, the editorial states prompts researchers to continue "(presenting) their work as necessary to the well-being of all members of society however they may vote."
I agree in principle with Nature’s article, but there’s another side to the story that we should not forget. Some of those noisy minorities are also very good at planning and implementing their own communication strategy, while scientists are not.

That’s why I beg to differ a bit from Nature’s prescription. Scientists should definitively present the utility of their work to the lay public, as Nature says, but do so with a communication strategy. Presenting exciting results was exactly what my egghead friends were doing at the Brussels meeting. Clearly, it didn’t work alone.

So, dear scientists, let me add a few modest communication tips on top of Nature’s:
  • Articulate a strategy. Because it’s what your opponents will do. 
  • Be realistic and hire an expert; effective communication requires specialized knowledge. Good news, there are many experienced communicators who are eager to work with good scientists (disclaimer: I am one of them). 
  • Structure your effort into a coordinated campaign, not just single meetings or dissemination events. Getting smart speakers together does not automatically make a strategy. When in doubt, do yourself a favor: call a pro.
Sergio Pistoi

[Two colleagues at CIRM did an informal review of the use of social media by opponents and proponents of embryonic stem cell research. What they found backed up Sergio’s contention. Those opposed have a more organized strategy and are better at “staying on message.” That study was published as part of the World Stem Cell Summit in 2011.]

Thursday, April 17, 2014

Dual Clinical Trial Announcements Offers New Hope for Treating Spinal Cord Injury

In a move that takes stem cell-based therapies for spinal cord injury one step closer in the long march from the lab bench to routine clinic use, StemCells, Inc., today announce that they have completed enrollment in a clinical trial that aims to treat chronic spinal cord injury.

This Phase I/II trial will evaluate the safety and early signs of effectiveness of the Company’s human neural stem cells in patients with varying degrees of injury. The cells that the company has branded HuCNS-SC were surgically transplanted into the enrolled patients. The Company is now monitoring changes in neurological function over a period of several years.

CIRM fostered this clinical trial by funding earlier basic research at the University of California at Irvine. Based in California, StemCells, Inc., states this trial holds promise for one day soon treating patients suffering from chronic spinal injury and paralysis. The Company’s Vice President Dr. Stephen Huhn said in a news release picked up by the Sacramento Business Journal:
"This is the first clinical trial evaluating stem cell transplantation in spinal cord injury to successfully complete enrollment. Successful dosing of all subjects in the trial is a major accomplishment for the field and the spinal cord injury program at StemCells, Inc.”
This advance comes on the heels of more clinical trial news from Neuralstem, Inc., and the University of California, San Diego School of Medicine. Yesterday they announced that the University’s review board had approval a Phase I trial to treat spinal cord injury patients with the company’s adult neural stem cells, NSI-566. This trial builds on successful results in animal models, which showed that paralyzed rats exhibited significant improvement in motor function—just days after being transplanted with the cells.

Neuralstem’s technology has already led to initially successful clinical trials in patients suffering from ALS, also known as Lou Gehrig’s disease. With the new spinal cord injury trial, the Company believes it can confirm a therapeutic strategy for reversing the debilitating effects of spinal injury. Karl Johe, Neuralstem's Chairman of the Board and Chief Scientific Officer, said in a recent news release picked up by Reuters: “
"With 30 successful spinal surgeries completed in our ALS trials, we feel we are ready to tackle spinal cord injury and are excited to begin this ground-breaking study.”
Researchers have often looked to regenerative medicine to treat conditions such as paralysis caused by spinal injury. Now, as companies like StemCells, Inc., and Neuralstem begin to move their technology from the lab and into patients, the long-held hopes of scientists, patients and their families is closer to becoming reality.

You can read about CIRM’s funded projects in the field in our spinal cord injury fact sheet.

Anne Holden

Wednesday, April 16, 2014

Genetically modified stem cells offer potential new path to treating Alzheimer’s disease

Dr. Mathew Blurton-Jones of U.C. Irvine: his new study may help open new approaches to Alzheimer's
The Holy Grail of medical research is to find a cure for deadly diseases. But in the case of diseases like Alzheimer’s, where we don’t even have any truly effective treatments, any research that offers the potential of a new approach to slowing the progression of the disease has to be considered an advance. That’s why research from the University of California at Irvine is encouraging news indeed.

One of the characteristics of Alzheimer’s is a build-up of plaques in the brain caused by too much of the protein amyloid-beta. It’s not known if that build-up is a cause or an effect of the disease but if it is a cause then, in theory at least, reducing that build-up could help stop or slow the progression of Alzheimer’s.

This is where an enzyme called neprilysin comes in. Neprilysin helps break down the accumulation of amyloid-beta. As researcher Dr. Mathew Blurton-Jones says in a news release:

"Studies suggest that neprilysin decreases with age and may therefore influence the risk of Alzheimer's disease. If amyloid accumulation is the driving cause of Alzheimer's disease, then therapies that either decrease amyloid-beta production or increase its degradation could be beneficial, especially if they are started early enough." 

So the researchers at U.C. Irvine took some neural or brain stem cells and genetically modified them so that they would produce 25 times more neprilysin than ordinary neural stem cells. They then injected them into two different kinds of mice that had forms of Alzheimer’s, targeting the areas that are most affected by the disease, the hippocampus and the subiculum.

The results, published in the journal Stem Cells Research and Therapy, showed some promising results. The mice given the genetically modified stem cells were found to have significantly reduced amounts of the amyloid-beta plaques in their brain. This result continued for at least one month after the transplant.

Now a lot of encouraging results in mice haven’t panned out in humans, but Dr. Blurton-Jones points out the importance of seeing this result in mice with two different forms of Alzheimer’s:

"Every mouse model of Alzheimer's disease is different and develops varying amounts, distribution, and types of amyloid-beta pathology. By studying the same question in two independent transgenic models, we can increase our confidence that these results are meaningful and broadly applicable to Alzheimer's disease."

 It still remains to be seen whether this approach will improve the functioning of the brain, that’s research that still has to be done, but it does suggest that it might offer a new approach to reducing the build-up of plaques in the brain, and so possibly slow the progression of the disease.

We have awarded almost $50 million in funding for more than a dozen different research projects focusing on finding ways to develop new treatments and even a cure for Alzheimer’s.

kevin mccormack

Tuesday, April 15, 2014

A placebo-controlled trial in cerebral palsy might unlock some answers for parents

The parents of children with cerebral palsy (CP) rank high in number among the desperate calls that come to CIRM wanting to know about stem cell therapies offered on the internet. They don’t like to hear that we have very little information suggesting benefit from stem cells in these kids and that there is little reason to believe the types of cells being offered could grow new brain tissue to repair the abnormal brain development seen in CP.

They like hearing that there is some evidence that the type of stem cells being used might be able to tamp down any inflammatory process that is hampering brain function, and that it might be possible for these cells to trigger some sort of innate repair mechanism within the child. But the bottom line is that we really don’t know, and we certainly don’t know what is the best cell type to use and how, when and where to deliver the cells to get the maximum benefit if there is any.

So, it was heartening to see that a clinical trial registered with the Food and Drug Administration is enrolling patients in a study designed to answer some of these questions. Sponsored by Cord Blood Registry and conducted at the University of Texas Health Sciences Center at Houston the trial will compare two types of stem cells that came from the children themselves. They will compare stem cells from some children’s own stored cord blood with stem cells from other children’s bone marrow.

The research team plans to recruit 15 children into each group and 10 in each will receive the stem cells and five will receive a placebo injection, containing no cells. The parents will not know which injection their children received but at the end of one year, the parents of those who received the placebo will be told and given the option of a stem cell injection.

The Los Angeles Business Journal was one of many outlets that picked up the company’s press release. In it, the lead researcher, UT’s Charles Cox, explained the effect they hoped to see: "There is preclinical data indicating that the ongoing neuro-inflammatory response is a driver of further injury in cerebral palsy so the hope is to reduce this neuro-inflammation. Our goal is to break the cycle of inflammation and injury." They plan to evaluate the children as six months, one year and 24 months. So, anxious parents may start to get a few answers in a year or so. CIRM convened a workshop on how stem cell science could impact CP and that cerebral palsy report is available online.

Don Gibbons

Monday, April 14, 2014

Changing landscape of funding stem cell therapies: not just a venture capitalist’s game

Entrepreneurs and researchers are finding new sources to cross the "valley of death" funding gap.
Neil Littman is the Business Development Officer at CIRM

In February I gave a talk at the Phaciliate Conference in Washington D.C. entitled Bridging the Funding Gap: Non-Profit and Industry Collaborations, CIRM’s Perspective. Phacilitate is an annual conference focused on the cell and gene therapy industry and attracts a variety of attendees from around the country. Beyond showcasing the latest technologies and scientific advancements, one of the major areas of focus of the conference is on raising money, collaborations and industry partnerships. The conference provides a great chance to reflect on the prior year’s activity and discuss the trends that may continue into the upcoming year.

One of the cornerstone pieces of my talk, and a theme I heard repeated throughout the conference, was the shift in the traditional funding continuum. What this means is that traditional sources of capital for early stage life science investments have shifted from venture capitalists to other sources of funding. Many life sciences focused venture funds have had a hard time raising new funds due to lackluster performance of their prior funds. This has served to shrink the available pool of venture capital and also consolidate it into the hands of those that have been able to raise new funds. Entrepreneurs and researchers have, therefore, had to look to other sources of capital to fund their research.

Fortunately, disease foundations have stepped in to help alleviate the funding gap. JDRF (the Juvenile Diabetes Research Foundation), for example, has become a significant source of funding for Type 1 diabetes. Their research funding has grown on an annual basis from a few hundred thousand dollars in the organization’s early years to over an estimated $110 million in 2012. In fact, CIRM has successfully partnered with JDRF to jointly provide over $50 million in funding to ViaCyte, a San Diego-based company developing an embryonic stem cell-derived product for the treatment of Type 1 diabetes.

In addition to disease foundations, venture philanthropists have become increasingly important in funding translational medicine and research. For example, in November 2013 Denny Sanford announced plans to donate $100 million to UC San Diego to accelerate discoveries in human stem cells into drugs and therapies to treat a wide range of diseases, from cancer to Alzheimer’s disease to neurological injury and stroke.

Finally, many large multinational pharmaceutical and biotechnology companies are looking at earlier stage opportunities in an effort to externalize R&D costs as a way to bolster lackluster pipelines beset by a plethora of late stage product failures. For example, Capricor, a CIRM grantee, recently announced a deal with Janssen (a division of Johnson & Johnson) for $12.5 million upfront and up to $300 million of potential milestones. CIRM is partially funding Capricor’s Phase 2 trial for myocardial infarction. Another example is Biogen Idec’s recent deal with another CIRM grantee, Sangamo Biosciences, in which Biogen agreed to pay Sangamo $20 million upfront and up to $300 million of potential milestones for the development of treatments for blood disorders. This includes the beta-thalassemia program funded under CIRM’s Strategic Partnership 2 Award.

It is imperative that CIRM leverage our resources with these other sources of capital in order to bring promising new therapies to patients and bridge the funding gap, often called the “valley of death”. Only by working together will we all be successful in delivering novel therapies to the patients who need them most.

-Neil Littman

Friday, April 11, 2014

Stem cell stories that caught our eye: cancer therapy with broad aim, lupus and politics again

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Attack on cancer stem cell advancing with a broad aim. Most of the advances in cancer in recent years require matching very specific therapies to a narrow set of patients with a specific genetic vulnerability—so called personalized cancer care. But this type of therapy is very expensive and frankly disappointing to the majority of patients who don’t fit the profile of responders. This week a CIRM-funded Disease Team was in the spotlight at the annual meeting of the American Association for Cancer Research for a therapy that has a very broad aim. The Stanford team plans to begin clinical trials later this year with a protein called an antibody that blocks a signal on the surface of cancer stem cells that inhibits our immune system’s ability to seek out and destroy tumors. The researchers have dubbed this signal the “don’t eat me gene” and this gene, CD47, seems to be present on a wide array of tumor types, which means the antibody might work in many cancers. It has in mice, but . . .

The cancer researchers are meeting in San Diego this year, and the San Diego Union Tribune ran a story about the Stanford presentation there. The clinical trial we will be funding with the therapy targets leukemia and you can read about our work to target those cancer stem cells in our leukemia fact sheet.

Cord Blood Benefit seen in lupus, but transient. medpageTODAY did a nice analysis of a study using stem cells from umbilical cord blood for treating lupus in patients that had failed conventional therapy. The Chinese team had used the mesenchymal type stem cells in the cord blood, which are known to have some anti-inflammatory properties. In the multicenter trial, 60 percent of the 40 patients who had received the stem cells had a major or partial clinical response to the therapy. But as usual with medpageTODAY, the author put the numbers in perspective. She noted that we don’t know what the cells do to elicit the response, and can only speculate that they secrete chemicals that tamp down the autoimmune reaction of the disease. Also, they noted that the cells do no stay in the patients for long periods and a third of the responders had relapsed within a year, suggesting the need for retreatment.

Scarless, baby-smooth wound healing possible? While it is easy to dismiss the social value of scarless wound healing—envisioning waiting rooms at cosmetic surgery centers—severe scaring can be very debilitating such as with severe injuries around the eyes or fingers. It turns out that babies are born with legendary soft skin, in part, because if they have any skin tears in the womb, their skin stem cells are different from our adult skin stem cells. They can heal wounds without any scaring. A team at Stanford has now isolated and identified these fetal skin stem cells opening up the possibility of finding out how they accomplish the scarless healing and replicating that method in adult tissue. Science Codex picked up a press release from the journal Advances in Wound Care and the release has a link to the free-access journal.

A week to remember the controversies underlying our field. Scientific American posted a blog this week with a nice time of the various actions by Congress and the executive branch that have impacted our ability to study and gain the benefits from stem cells. Then Nature posted a blog announcing that the National Institutes of Health had closed its center dedicated to stem cell research for no disclosed reason, although there is much buzzing in the community. Next, Inside Science posted that the anti-embryonic stem cell forces in the European Union had gathered enough signatures to put a measure on the ballot there. Then today, numerous outlets ran a story about South Carolina joining the long list of states that have introduced “personhood” legislation that would declare a fertilized egg a person and end up banning much stem cell research. Here is a version from the Charlotte Observer. Let’s hope the voters in this state, like every prior state where the measure has been introduced, muster the will to defeat it.

Don Gibbons

Thursday, April 10, 2014

Living proof exercising the brain helps it function, provides clues to improving stem cell therapy

Get in that wheel and exercise little guy; it's good for your brain.
We have long known the brain is not static. Parts of it change and become stronger in response to being stimulated. This “plasticity” as it is called, is generally attributed to changes in the nerves themselves. But a CIRM-funded Stanford team now has proof that strengthening the insulating myelin that wraps the nerves may have a critical role in this plasticity. Think of it as improving the roadbed for the signals being sent along the nerve highway.

A few recent studies have suggested this role for myelin, but they have looked at nerves growing in a lab dish. The tests that could have proved this is really happening in living animals have been too invasive until now. The Stanford team, led by Michelle Monje, used a new technique called optogenetics to make the connection in living mice. The procedure inserts the genes for light-sensitive neural switches into specific nerves. Those nerves then fire when researchers expose them to certain wavelengths of light. Because the light can diffuse through the brain from the surface, no invasive probes are necessary.

In this case, the light became the brain’s exercise bike. The nerves that had the added gene were the motor nerves, and after a period of stimulation the researchers saw myelin growth and in the following weeks improved muscle function in the mice.

Monje’s team attributed the improved myelin status to activity of a type of cell called an oligodendroctye precursor cell, which is the type of brain cell many stem cell scientists target for transplanting into patients. In stem cell therapy, many researchers consider it better to transplant these middle-man cells created from stem cells rather than the stem cells themselves. The current study gives the stem cell community ways to think about improving the results after transplant. Following up with brain stimulation may be important.

A press release from Stanford quotes Monje on the broad implications for her finding:
“Myelin plasticity is a fascinating concept that may help to explain how the brain adapts in response to experience or training. . . and future work on the molecular mechanisms responsible may ultimately shed light on a broad range of neurological and psychiatric diseases.”
In the CIRM-funded project using these findings, Monje’s goal is to find small molecules that could stimulate the activity of the oligodendrocyte precursor cells in patients who have undergone chemotherapy and are experiencing the mental decline dubbed “chemo brain.” The researchers’ findings are described in a paper that was published online today in Science Express.

Don Gibbons

CIRM funding: RN3-06510