For several decades investigators have been addressing the tantalising question, is there a hepatic stem cell?1Despite widespread attempts to identify and characterise such cells in the liver and a plethora of papers, reviews, and monographs on the subject,2-4 doubts as to their very existence have remained. It is only relatively recently that these doubts have been removed, at least in the eyes of most investigators, with convincing evidence from rodent studies and novel developments in the cell biology of the pathogenesis of human liver disease. Moreover, new exciting findings indicate that in tissues, including bone marrow and the brain, there reside cells with an innate ability to differentiate into divergent cell types. The stem cell field is currently a “hot” topic.

Although essentially a quiescent organ, the normal adult liver can fully regenerate following surgical resection or injury. Much of what we have learned about liver growth control derives from the classical two thirds partial hepatectomy model in the rat. The process begins with growth activation of mature hepatocytes; other cell types, including biliary epithelial cells (BEC) and sinusoidal cells, proliferate with a delayed response.5 However, if liver damage is so severe that hepatocytes are largely obliterated or for some reason are prevented from entering the growth cycle by exposure to hepatotoxins or carcinogens, then activation of a liver stem (progenitor) cell population is postulated,2 3 giving rise to so-called “oval” cells. These cells are thought to have both clonogenic and bipotential capacity—that is, the ability to proliferate and differentiate into cells of either hepatocyte or BEC lineage.6 7 There is also evidence that under certain conditions oval cells can be induced to differentiate into non-hepatic lineages including intestinal and pancreatic epithelium.3The origin of oval cells and their precise location within the …