Scientists have found a way to transform skin cells into fully functional liver cells that can grow on their own, giving hope to millions of people worldwide who suffer from liver failure.
In the study "Mouse liver repopulation with hepatocytes generated from human fibroblasts", published in the journal Nature Feb. 23, researchers genetically engineered skin cells so they resemble endoderm cells which mature into different body organs.
"Instead of taking the skin cells back to the beginning, we took them only part way, creating endoderm-like cells," said study author Saiyong Zhu, from the Gladstone Institute of Cardiovascular Disease in California. "This step allowed us to generate a large reservoir of cells that could more readily be coaxed into becoming liver cells."
The researchers then utilized a set of genes and compounds to transform the cells into liver cells. After a few weeks, they observed that the cells began to take the form and even started to perform like liver cells. The early-stage liver cells were then transplanted into the livers of mice and monitored.
"Earlier studies tried to reprogram skin cells back into a pluripotent, stem cell-like state in order to then grow liver cells," explained study co-author Sheng Ding, from the Gladstone Institute. "However, generating these so-called induced pluripotent stem cells, or iPS cells, and then transforming them into liver cells wasn't always resulting in complete transformation. So we thought that, rather than taking these skin cells all the way back to a pluripotent, stem cell-like state, perhaps we could take them to an intermediate phase."
The researchers found that the human liver protein levels in the mice increased which means that the transplanted cells were transforming into mature and functional liver cells. They also observed that the cell growth did not slow down nine months after the transplant indicating they have found a way to regenerate liver tissue.
"Our results establish the feasibility of significant liver repopulation of mice with human hepatocytes generated in vitro, which removes a long-standing roadblock on the path to autologous liver cell therapy," the researchers wrote.
Study co-author Holger Willenbring, associate director of the UCSF Liver Center, said the results of their research were promising.
"Many questions remain, but the fact that these cells can fully mature and grow for months post-transplantation is extremely promising," Willenbring said. "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."
