A population of liver cells has been found that are better at regenerating liver tissue than hepatocytes. The study is the first to identify these so-called ‘hybrid hepatocytes,’ and show that they are able to regenerate liver tissue without giving rise to cancer.
Of all major organs, the liver has the highest capacity to regenerate – that’s why many liver diseases, including cirrhosis and hepatitis, can often be cured by transplanting a piece of liver from a healthy donor. The liver’s regenerative properties were previously credited to a population of adult stem cells known as oval cells. But recent studies concluded that oval cells don’t give rise to hepatocytes; instead, they develop into bile duct cells. These findings prompted researchers to begin looking elsewhere for the source of new hepatocytes in liver regeneration.
In this latest study, led by Prof Michael Karin, researchers traced the cells responsible for replenishing hepatocytes following chronic liver injury induced by exposure to CCl4, a common environmental toxin. That’s when they found a unique population of hepatocytes located in the portal triad. These special hepatocytes, undergo extensive proliferation and replenish liver mass after chronic liver injuries. Since the cells are similar to normal hepatocytes, but express low levels of bile duct cell-specific genes, they were labeled “hybrid hepatocytes.”
Meanwhile, many other research labs around the world are working on ways to use induced pluripotent stem cells (iPSCs) to repopulate diseased livers and prevent liver failure. “Although hybrid hepatocytes are not stem cells, thus far they seem to be the most effective in rescuing a diseased liver from complete failure,” said Joan Font-Burgada, PhD.
While iPSCs hold a lot of promise for regenerative medicine, it can be difficult to ensure that they stop proliferating, ie have high risk of tumors. To test the safety of hybrid hepatocytes, Karin’s team examined 3 different mouse models of liver cancer. They found no signs of hybrid hepatocytes in any of the tumors, leading the researchers to conclude that these cells don’t contribute to liver cancer caused by obesity-induced hepatitis or chemical carcinogens. “Hybrid hepatocytes represent not only the most effective way to repair a diseased liver, but also the safest way to prevent fatal liver failure by cell transplantation,” Karin said.
http://health.ucsd.edu/news/releases/Pages/2015-08-13-cells-regenerate-liver-without-tumors.aspx
Hybrid hepatocytes (HybHP) constitutively reside in portal triads of healthy liver •HybHP can replenish the entire parenchyma after chronic hepatocyte damage •Despite multiple divisions, HybHP do not originate HCC in three independent models •HybHP exhibit unmatched regenerative capacity in a diseased liver
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