LIVER STEM-CELLS - WHEN THE GOING GETS TOUGH THEY GET GOING

The ability of the liver to regenerate is widely acknowledged, and thi s is usually accomplished by the entry of normally proliferatively qui escent hepatocytes into the cell cycle. However, when hepatocyte regen eration is impaired, small bile ducts proliferate and invade into the adjacent hepatocyte parenchyma. In humans and experimental animals the se ductal cells are referred to as oval cells, and their association w ith defective regeneration has led to the belief that they are the pro geny of facultative stem cells. Oval cells are of great biological int erest since they may represent a target population for hepatic carcino gens, and they may also be useful vehicles for ex vivo gene therapy fo r the correction of inborn errors of metabolism. The ability of oval c ells to differentiate into hepatocytes has been demonstrated unequivoc ally. However, this process only occurs when the regenerative capacity of hepatocytes is overwhelmed, and thus, unlike the intestinal epithe lium, the river is not behaving as a classical continually renewing st em cell-fed lineage.