Friday, October 4, 2013

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

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.

Following a trend from recent months, my full report talks about work by teams that are making major progress toward creating complex tissues, not single layers of cells growing a lab dish, but three-dimensional tissues with multiple types of cells. These complex tissues are the type of construct we need to perfect if we are going to be able to grow tissues for organ repair. This month’s studies dealt with brain and pancreas tissues.

I want to devote this blog to a different paper; one that is really basic science. This paper gives us a tool for investigating several fundamental questions that have really slowed down our progress to the clinic in many ways. We really don’t understand what is going on in the cell when we use various genetic factors to reprogram adult cells to become iPS type stem cells. A team at the Weizmann Institute published a paper in Nature in September that provides us with a system that should allow us to tease out what is happening in reprogramming. That should make iPS technology much more practical.

Shinya Yamanaka deservedly won the Nobel prize in 2012 for his 2006 discovery of how to make induced Pluripotent Stem cells (iPS cells). But his process was quite inefficient and slow. So ever since, hundreds of teams have tried to improve the efficiency and speed of the process, and the in the past six years they have had only marginal success. Now, the Weizmann team leap-frogged the pack. Instead of maybe one percent of adult cells exposed to the reprogramming factors converting to iPS cells, they got nearly 100 percent. And instead of taking four to six weeks, it took one.

The efficiency is nice, but if you are trying to make personalized, immune compatible repair cells for a patient, you only need one stem cell line. The speed could be critical if a patient has an acute injury such as heart attack or stroke. But the real advance that can propel this field as a whole is the fact that cells moved to the stem cell fate in a synchronized way. On day one they all had turned on the same set of genes, and on day three, a slightly different set of genes was being used by each cell, etc.

With reprogramming prior to this, researchers always had a mixed soup of cells that were at different stages of reprogramming and even more cells that had gone part way down the reprograming path and stopped. With this hodgepodge of cells it was impossible to sample DNA from cells and see which genes should be turned on at any stage to get proper reprogramming. Now we should be able to create a genetic road map to reprogramming.

However, the real value of that road map may not be in creating iPS cells. Many in field think one ultimate goal of stem cell science is to reprogram adult cells directly in the patient. But you would not want to reprogram them all the way back to pluripotent cells like iPS cells. You would want to stop the reprogramming at an intermediate state, perhaps a progenitor for brain tissue that could mature into both neurons and support cells. This technology should allow us to create recipes that will reprogram cells to a specific desired end point. It will take much more work, but this opens the door.

If you want a primer on iPS technology my colleagues have created and posted a video on creating iPS cells.

My full report is available online, along with links to my reports from previous months.

Alan Trounson

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