The liver is the most regenerative organ in adult mammals. Unlike any other organ, it is possible to cut out sections and the liver will regrow the lost tissue. The regrowth isn't perfect, unlike the case in highly regenerative species such as salamanders and zebrafish, but it does produce functional liver tissue. What makes the liver different? Despite a great deal of interest and activity in the research community, that question is nowhere near being comprehensively answered. Will practical regenerative therapies for the liver emerge before regenerative therapies for other organs? Maybe, maybe not. So far there is little sign that work on the liver is racing ahead of work on the rest of the portfolio of internal organs.

Today's open access paper is a recent output from just one line of investigation into liver regeneration, among the many lines that are presently ongoing. While the search for stem cell like populations in adult liver tissue is the focus here, with hybrid hepatocytes as the starting point, other research groups are looking into alternative splicing and the Hippo pathway that influences regeneration in a number of organs, or the subset of liver cells that express telomerase, behavior usually reserved for stem cells in the human body. It remains to be seen which lines of work will give rise to the next generation of regenerative medicine for the liver.

Liver transplants could be redundant with discovery of new liver cell

Scientists have identified a new type of cell called a hepatobiliary hybrid progenitor (HHyP), that forms during our early development in the womb. Surprisingly, HHyP also persists in small quantities in adults and these cells can grow into the two main cell types of the adult liver (Hepatocytes and Cholangiocytes) giving HHyPs stem cell-like properties. The team examined HHyPs and found that they resemble mouse stem cells which have been found to rapidly repair mice liver following major injury, such as occurs in cirrhosis. "For the first time, we have found that cells with true stem cell-like properties may well exist in the human liver. This, in turn, could provide a wide range of regenerative medicine applications for treating liver disease, including the possibility of bypassing the need for liver transplants. We now need to work quickly to unlock the recipe for converting pluripotent stem cells into HHyPs so that we could transplant those cells into patients at will. In the longer term, we will also be working to see if we can reprogramme HHyPs within the body using traditional pharmacological drugs to repair diseased livers without either cell or organ transplantation."

Single cell analysis of human foetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors