Wednesday, February 6, 2013

Alan Trounson's monthly picks: advances in reprogramming

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.

My report this month is filled with examples of researchers improving our ability to reprogram one type of cell to become another type of cell. While this may seem routine by now, doing it efficiently and understanding the results is far from routine.

One team introduced a single genetic factor and was able to show in newborn mice that a brain cell already destined to become one type of nerve can be coaxed to become a completely different type of nerve. Since it was done in living animals it opens the possibility of working with patients that have one type of nerve destroyed, and seeing if we can convert neighboring nerves of a different type to the type lost by disease.

That team was working on nerve-to-nerve conversions, but another team made significant advances in the more difficult task of reprogramming unrelated tissue, such as skin, to become nerves. While other teams have accomplished this, they have all used fairly complex mixes of reprogramming factors. The current team did it with just one. This would make it much simpler to attempt these conversions in a patient both in terms of the science, but also the ease of regulatory approval if you are introducing a single factor into the patient instead of several.

Another team used the more standard technology of turning adult cells into embryonic-like stem cells called iPS cells. But they started with immune system cells from patients with cancer and HIV. In particular, they used T cells that had been taught by the immune system to attack the cancer or the virus. These T cells sometimes fail to get the job done because they get overwhelmed by fast growing tumors or persistent invaders like HIV. The immune system can’t produce enough of the targeted T cells. Part of this is because the ends of the chromosomes that help cells multiply get worn down as we age. The iPS reprogramming process appears to rejuvenate those chromosome tips called telomeres to a more youthful form. The result was that when the iPS cells made from T cells were matured back into T cells, those cells could multiply in sufficient numbers to augment a patient’s immune response, although that has not been tried in patients yet.

In one surprising paper, it looks like even one type of bacteria gets into the reprogramming act. The bacteria, the one that causes leprosy, initially infects a type of nerve cell outside our central nervous system. It then reprograms those cells into a type of stem cell that can carry the bacteria around the body and help the infection spread. Knowing this can offer targets for therapy, but also provides clues to improving the broader field of cell reprogramming.

Last, I want to note the paper that leads the full report this month. There has been some controversy in the field about whether or not iPS cells made from a patient’s own tissue could be turned into a desired repair tissue, injected back into the patient, and avoid attack by the immune system. A much-discussed paper in 2011 suggested this might not be possible. In January, a team in Boston reported on a well-designed study that arrived at the opposite result. They found no rejection of adult tissue derived from iPS cells. This is very reassuring, but probably not the final word on this key issue.

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

A.T.

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