For patients with end-stage liver disease, a liver transplant is the only viable option to stave off death. Liver failure is the 12th leading cause of death in the United States, and finding a way to regenerate failing livers is one of the Holy Grails of liver research. New research suggests that one it will be feasible to use a patient’s own cells to regenerate their liver.
Researchers at the Icahn School of Medicine at Mount Sinai have discovered that a particular human embryonic stem cell line can be differentiated into a previously unknown liver progenitor cell that can differentiate into mature liver cells.
“The discovery of the novel progenitor represents a fundamental advance in this field and potentially to the liver regeneration field using cell therapy,” said Valerie Gouon-Evans, the senior author of this study and assistant professor of medicine at the Icahn School of Medicine. “Until now, liver transplantation has been the most successful treatment for people with liver failure, but we have a drastic shortage of organs. This discovery may help circumvent that problem.”
Gouon-Evans collaborated with the laboratory of Matthew J. Evans and showed that the liver cells that were made from the differentiating liver progenitor cells could be infected with hepatitis C virus. Since this is a property that is exclusive to liver cells, this result shows that these are bona fide liver cells that are formed from the progenitor cells.
One critical step in this study was the identification of a new cell surface protein called KDR, which is the vascular endothelial growth factor 2. KDR was thought to be restricted to blood vessels, blood vessels progenitor cells (EPCs), and blood cells. However, the Evans / Gouon-Evans study showed that activation of KDR in liver progenitor cells caused them to differentiate into mature liver cells (hepatocytes). KDR is one of the two receptors for VEGF or vascular endothelial growth factor. Mutations of this gene are implicated in infantile capillary hemangiomas.
The next step in this work is to determine if liver cells formed from these embryonic stem cells could potentially facilitate the repair of injured livers in animal models of liver disease.