New “backup” liver repair mechanism

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New study reveals cells can be reprogrammed to repair severe liver injury.

The research shows bile duct cells can switch to become normal liver cells to help repair the liver after severe damage. Understanding how this back-up system is controlled could pave the way for new liver therapies.

For the new study, published in Nature, CRM scientists studied hepatocytes, the main cell type found in the liver. Hepatocytes play a key role in cleaning toxic substances from the blood stream. After minor damage, hepatocytes can multiply to repair the damage, but if the injury is too severe the cells cannot cope and they stop proliferating. This can lead to chronic liver disease.

The researchers, including Centre members Wei-Yu Lu and Alex Raven as joint first authors, developed a system to mimic chronic liver disease in mice. After severe liver injury, another type of cell in the liver, called cholangiocytes, were reprogrammed to become hepatocytes. The cholangiocytes are specialised cells that line bile ducts in the liver. These cells normally regulate the secretion of bile, a fluid that helps break down fats from food.

By transforming into functional hepatocytes, the bile duct cells served as a back-up to help repair damaged liver tissue.The team say their findings pave the way to develop drugs that encourage bile duct cells to become hepatocytes to help repair liver tissue. Lead researcher Professor Stuart Forbes, Director of the MRC-CRM, said:

This is the first conclusive proof that bile duct cells can serve as an important back-up system to help repair damaged liver tissue. We think this back-up system is helping the liver to repair, but under severe strain it might not be enough.

So we plan to do screens of clinically approved drugs on human bile duct cells to see if they can increase their regenerative capacity. We’re hopeful that understanding the signals that trigger these cells to behave this way could lead to new therapies to help repair damaged livers before the livers fail completely.”

Liver disease is the one of the top five causes of premature death in the UK. Chronic liver disease can have many causes, including viruses such as hepatitis, toxicity from drugs such as paracetamol, and non-alcoholic fatty liver disease.

The research was funded by the Medical Research Council (MRC) and the UK Regenerative Medicine Platform, a partnership between the Biotechnology and Biological Sciences Research Council (BBSRC), the Engineering and Physical Sciences Research Council (EPSRC) and the MRC.

DOI: 10.1038/nature23015

Image credit: Alex Raven