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| Courtesy of the National Library of Medicine |
Scientists have succeeded in reprogramming skin cells to closely resemble heart cells, pancreas cells and even neurons, but generating stem cell-derived liver cells posed a challenge. Now, researchers at the Gladstone Institutes and the University of California, San Francisco, have found a way to transform skin cells into fully functioning mature liver cells that grow on their own after being transplanted into mice.
The research has implications for patients with liver failure, for which the only treatment option available is a costly liver transplant.
In previous liver-cell reprogramming studies, scientists had difficulty getting stem cell-derived liver cells to survive once they were transferred into existing liver tissue. Instead of reprogramming skin cells back to a pluripotent, stem cell-like state to then grow liver cells, the Gladstone-UCSF team used a "cocktail" of reprogramming genes and chemical compounds to transform human skin cells into cells that mimicked the endoderm--cells that eventually mature into many of the body's major organs, including the liver.
Researchers used a set of genes and compounds they identified that can transform endoderm cells into functioning liver cells. After a few weeks, the cells began to turn into liver cells. They then transplanted these early-stage liver cells into the livers of mice, monitoring growth and function over the next 9 months. Two months after transplantation, the team observed a spike in human liver protein levels in the mice, a sign that the new cells were turning into mature, functional liver cells. Nine months into the experiment, cell growth continued.
The findings, which were published online Feb. 23 by Nature, indicate a possible way to regenerate liver tissue.
"Many questions remain, but the fact that these cells can fully mature and grow for months post-transplantation is extremely promising," said Dr. Holger Willenbring, associate director of the UCSF Liver Center and one of the study's senior authors, in a statement. "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."
- here's the press release
- see the Nature abstract