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Hybrid Hepatocytes in Liver Regeneration

The liver is the most regenerative of organs, capable of regrowing lost sections even in mammals. Here researchers identify a novel population of cells that contributes to that capacity for regrowth, and which might prove to be the basis for regenerative therapies:

The mechanisms that allow the liver to repair and regenerate itself have long been a matter of debate. 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.

Researchers traced the cells responsible for replenishing hepatocytes following chronic liver injury induced by exposure to carbon tetrachloride, a common environmental toxin. That's when they found a unique population of hepatocytes located in one specific area of the liver, called the portal triad. These special hepatocytes, the researchers found, 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, the researchers called them "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. While iPSCs hold a lot of promise for regenerative medicine, it can be difficult to ensure that they stop proliferating when their therapeutic job is done. As a result, iPSCs carry a high risk of giving rise to tumors. To test the safety of hybrid hepatocytes, the team examined three 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. "Although hybrid hepatocytes are not stem cells, thus far they seem to be the most effective in rescuing a diseased liver from complete failure. 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."

Link: http://health.ucsd.edu/news/releases/Pages/2015-08-13-cells-regenerate-liver-without-tumors.aspx

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