Skin cells can now be transformed into mature, fully functioning liver cells, thanks to a research team at the Gladstone Institutes and the University of California, San Francisco (UCSF).
Regenerative medicine has allowed skin cells to change into heart cells, pancreas cells and even neurons, but past studies had difficulty getting them to resemble liver cells because the cells failed to survive once transplanted into existing liver tissue.
The research team, led by Dr. Sheng Ding and UCSF Associate Professor Holger Willenbring, found a way to solve this problem using a new cellular reprogramming method.
Unlike past attempts, Ding and colleagues took the skin cells back to an intermediate phase of the transformation process, rather than going all the way back to a stem cell-like stage. The new technique involved using a "cocktail" of reprogramming genes and chemical compounds to transform human skin cells into cells that resembled the endoderm and intermediate phase. Endoderm cells are cells that eventually mature into many of the body's major organs, including the liver.
"Instead of taking the skin cells back to the beginning, we took them only part way, creating endoderm-like cells," Gladstone and CIRM Postdoctoral Scholar Dr. Saiyong Zhu, one of the paper's lead authors, said in a statement. "This step allowed us to generate a large reservoir of cells that could more readily be coaxed into becoming liver cells."
Once the team noticed that the cells were on their way to fully maturing into liver cells, they tested the method in the liver cells of mice. Over nine months, they monitored cell function and growth by measuring levels of liver-specific proteins and genes. After just two months post-transplantation, there was a noticeable boost in human liver protein, indicating that the transplanted cells were becoming mature, functional liver cells.
The paper's senior author, Dr. Willenbring, associate director of the UCSF Liver Center, sees only positive implications of this practice in the future.
"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," he said.
