Turning skin into mature liver cells. And they work!

It’s one thing to get a stem cell to turn into something that closely resembles another kind of cell, say a heart cell. But it’s another thing altogether to get it to change into a cell that not only resembles another cell, but acts exactly like it too. That’s what CIRM-funded researchers at the Gladstone Institutes have done with liver cells.

It’s a tricky process, but an essential one if you want to develop new therapies. Previous attempts with liver had come close, but none of the cells were able to survive and function after being transplanted into existing liver tissue. So the researchers at Gladstone, led by Sheng Ding, Ph.D., developed a new multi-step process to change ordinary skin cells into fully mature, adult liver cells.

Their findings are published in the latest issue of the journal Nature

Step One: Instead of taking a skin cell and, by manipulating a series of genes, turning it all the way back to an embryonic-like state, they reprogrammed the skin cell and transformed it into endoderm – a cell type that helps makes up many of our organs, including the liver.

Step Two: Using a set of genes and compounds they were able to change these endoderm cells into functioning liver cells.

Step Three: They transplanted these newly created liver cells into mice and over the next nine months were able to measure increased levels of human liver proteins in the mice, a clear sign the transplanted cells had become mature liver cells and were working.

In a news release  another CIRM-funded researcher Holger Willenbring, M.D., Ph.D., an Associate Professor at the University of California San Francisco, and one of the senior author’s of the paper, talked about the potential significance of their findings:

“Many questions remain, but the fact that these cells can fully mature and grow for months post-transplantation is extremely promising. In the future, our technique could serve as an alternative for liver-failure patients who don’t require full-organ replacement, or who don’t have access to a transplant due to limited donor organ availability.” 

According to the American Liver Foundation there are around 17,000 Americans waiting for a liver transplant. Every year around 1,500 people die waiting for a donated liver to become available.

Dr. Willenbring is also featured in a CIRM Spotlight on Liver Disease.

kevin mccormack