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 report discusses two different approaches to getting our own cells to do a better job of regenerating tissue needed to repair cellular damage¬—at least in mice. One team found a way to get poorly functioning old muscle stem cells to behave more like vigorous young muscle stem cells. In the other, a team developed a way to get heart muscle cells next to the site of heart attack damage to revert to a less mature state so that they can multiply and repair the damage.
However, I want to devote my blog this month to a different tissue, one that has been very difficult to regenerate using stem cells, the liver. While several teams have produced liver cells from pluripotent stem cells, either iPS type or embryonic stem cells, the resulting cells have had two flaws. They don’t mature fully and provide all the functions of normal liver and they don’t proliferate after they are transplanted. In order to transplant cells into a severely damaged or genetically defective liver and have them restore its function, the cells would need to do both.
The CIRM-funded team at the University of California, San Francisco and the Gladstone Institutes developed a method to directly reprogram human skin cells into an intermediate state, neither iPS stem cell or adult liver cell. Those endoderm cells could be expanded extensively in the lab and then matured part way toward becoming adult liver cells before transplanting into a mouse model of liver failure. About two months after transplant the cells had matured to the point the researchers could detect proteins normally produced by human liver in the mice. Up to nine months later they detected continuously increasing amounts of the protein indicating continued growth and expansion of the human liver cells.
The lab portion of the procedure is potentially efficient enough to create liver cells from a patient’s own tissue that would be genetically matched, and possibly genetically corrected, and would be less likely to be rejected by the patient’s own immune system. The work points to a potential path for personalized liver repair.
My full report is available online, along with links to my reports from previous months.