Study identifies cell that repairs damaged liver tissue
A study has pinpointed a type of liver cell that mediates wound closure following damage to liver tissue.
It is widely known that the liver can regenerate itself following injury. However, in some cases of acute liver failure, this process can be challenging, rendering a liver transplantation as the only curative treatment option. A collaborative international study lead by the University of Edinburgh (UK), set out to understand the intricacies of the liver regeneration process, hoping to help inform the design of potential regenerative therapies.
In the study, the team examined human liver tissue samples derived from patients with acute liver failure. They found that although the liver cells had the capacity to regenerate, there were still significant areas of damage, indicating that liver regeneration does not solely consist of hepatocyte proliferation, but includes other mechanisms and processes to facilitate the complex process.
By combining single-nucleus RNA sequencing with spatial profiling, the team generated a comprehensive map known as a single-cell, pan-lineage atlas of the liver regeneration process. This was created by profiling genes within liver cells from both healthy and regenerating liver tissue. The team found that a population of wound-healing liver cells, known as the ANXA2+ migratory hepatocyte subpopulation, emerged during the liver regeneration in both humans and mice, playing a role in facilitating the process.
Further experiments in a mouse model of acetaminophen-induced liver injury revealed that motile liver cells drive the process of wound healing at the edge of the necrotic area, leading to restoration of the hepatic microarchitecture.
In patients with acute liver failure, the risk of infection remains a concern, as a breakdown of the gut–liver barrier can lead to bacteria entering the damaged liver. Interestingly, the team found that in the mouse model, the process of wound closure preceded hepatocyte proliferation, suggesting this order occurs to restore the barrier and prevent the spread of bacteria.
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Commenting on the significance of the study, lead author Neil Henderson (University of Edinburgh) stated that, “cutting-edge technologies have allowed us to study human liver regeneration in high definition for the first time, facilitating the identification of a cell type that is critical for liver repair. We hope that our findings will accelerate the discovery of much-needed new treatments for patients with liver disease.”
The study marks a significant step in fully understanding the process of liver regeneration and the potential to further boost liver damage recovery through these newly discovered wound-healing liver cells, paving the way for the development of novel therapeutics.