Regeneration mechanism discovered in mice could provide target for drugs to combat chronic liver disease


05-11-2019
Images show the TET1 epigenetic mark within the cells in an adult liver organoid  Credit: Luigi Aloia and Ludovica Bastianini

A newly-discovered molecular mechanism that allows damaged adult liver cells to regenerate could pave the way for drugs to treat conditions such as cirrhosis or other chronic liver diseases where regeneration is impaired. 

The mechanism, identified in mice, was discovered by researchers at the University of Cambridge’s Gurdon Institute.

It has long been known that the human liver is one of the organs that can regenerate its own tissue after short-term injury. But chronic damage in conditions such as alcohol abuse, fatty liver disease and certain viral infections, leads to impaired regeneration and cirrhosis (scarring), with eventual loss of liver function. 

The molecular mechanisms by which adult liver cells trigger the regenerative response, and how this fails in chronic liver disease, remain largely unknown. Around 30 million people across Europe suffer from chronic liver diseases, for which there is currently no cure, with liver transplants being the only treatment for liver failure. Scientists are therefore exploring how to trigger the intrinsic regenerative capacity of the liver, as an alternative means to restore function.

Researchers used mice and liver organoids ('mini-livers' generated in the lab from mouse liver cells) to study adult liver regeneration. They discovered that a molecule called TET1 is produced in healthy adult liver cells during the first steps of regeneration, and that this process is mimicked in liver organoids, where it has a role in stimulating organoid growth. The work is described in a paper published in the journal Nature Cell Biology.

Dr Luigi Aloia, first author of the paper and postdoctoral researcher at the Gurdon Institute, said: “We now understand how adult liver cells respond to the changes caused by tissue injury. This paves the way for exciting future work to boost cell regeneration in chronic liver disease, or in other organs where regeneration is minimal such as the brain or pancreas." 

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Images show the TET1 epigenetic mark within the cells in an adult liver organoid

Credit: Luigi Aloia and Ludovica Bastianini

Reproduced courtesy of the University of Cambridge

 

 

The University of Cambridge is acknowledged as one of the world's leading higher education and research institutions. The University was instrumental in the formation of the Cambridge Network and its Vice- Chancellor, Professor Stephen Toope, is also the President of the Cambridge Network.

University of Cambridge (cam.ac.uk)