Cell Surface Receptor Guides Liver Development

Identification of a growth factor that directs the differentiation of liver progenitor cells into mature liver cells may pave the way for development of laboratory-grown livers for use in organ transplants that will eliminate the need for living or deceased donors.

Investigators at Mount Sinai School of Medicine (New York, NY, USA) worked with mice and with samples taken from human fetal livers. They discovered that human embryonic stem cells could be differentiated into liver progenitor cells and produce mature liver cells as long at the cells expressed the cell surface growth factor KDR (kinase insert-domain receptor, also known as vascular endothelial growth factor receptor 2).

Vascular endothelial growth factor (VEGF) is a major growth factor for endothelial cells. The KDR gene encodes one of the two receptors of VEGF. This receptor, known as kinase insert-domain receptor, is a type III receptor tyrosine kinase. It functions as the main mediator of VEGF-induced endothelial proliferation, survival, migration, tubular morphogenesis, and sprouting. The signaling and trafficking of this receptor are regulated by multiple factors.

The investigators found that the newly differentiated liver cells were fully functional as demonstrated by their ability to be infected by the Hepatitis C virus, a property restricted to liver cells exclusively. KDR-positive progenitor cells were found in both human and mouse liver samples, indicating their importance in the formation of the organ.

"The discovery of the novel progenitor represents a fundamental advance in this field and potentially to the liver regeneration field using cell therapy," said senior author Dr. Valerie Gouon-Evans, assistant professor of developmental and regenerative biology at the Mount Sinai 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."

The study was published in the June 6, 2013, online issue of the journal Cell Stem Cell.

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