New Stem Cells Identified for Regenerating Liver Tissue

Hepatology, November 14, 2008

Researchers at the University of Pennsylvania School of Medicine have discovered a novel protein marker which identifies adult liver stem cells. Led by Dr. Linda Greenbaum, assistant professor of medicine in the Division of Gastroenterology, the scientists found that cells which express the marker can differentiate not only into liver tissue but also into the types of cells that line the bile duct. Known as FoxL1, the marker will allow for the isolation and expansion of these stem cells, which offer great hope for the treatment of patients who suffer from chronic liver disease. According to the American Liver Foundation, there are currently over 17,000 people in the U.S. alone who are on waiting lists for liver transplants, and who significantly outnumber donors.

As Dr. Greenbaum explains, "In a healthy liver, the proliferation of mature liver and bile-duct lining cells is sufficient to maintain the necessary size and function of the organ. This even works when the liver is confronted with mild and acute injury, but the situation changes when injury to the liver is chronic and severe." In more severe cases, the chronically injured liver tissue transmits chemical signals which in turn stimulate the proliferation of stem cells which eventually differentiate into new liver cells, though not usually in adequate amounts for complete healing. The newly discovered dual-potential liver stem cells which express the FoxL1 protein, and which were successfully associated with new liver fibroblasts in two mouse models, could be isolated and expanded in the laboratory and administered to patients therapeutically.

According to Dr. Greenbaum, "At this point, we haven't identified the molecular targets that are regulated by FoxL1 in the liver stem cell." Nevertheless, she adds, "This work has significant implications for cell-replacement therapies of chronic liver disease in the future."