The search for liver stem or progenitor cells has a long history, but there is now sufficient evidence to indicate that such cells do exist in adult animals and probably also in humans (see Refs. 1-6 for reviews). They constitute a reserve compartment that is activated in situations of severe liver injury in which hepatocytes cannot mount an appropriate proliferative response. Proliferation of cells of this compartment is seen at the early stages of hepatocarcinogenesis induced by many chemicals as well as in noncarcinogenic toxic injury, such as that produced by galactosamine administration. The nonparenchymal epithelial cells that can be detected in these conditions received the name “oval cells” because of their shape. Oval cells are not, however, a homogeneous population, but rather form a cellular compartment that contains cells at various stages of differentiation, either in the hepatocyte or bile duct lineages. A very small proportion of these cells seem capable of serving as progenitors for both lineages and could be considered to be stem cells , , , , , .

The search for liver stem cells, which started with the analysis of cell lineages in hepatocarcinogenesis, has now been extended to encompass work in fetal and adult normal livers as well as acutely injured liver. The central concept that emerged from these studies is that the adult liver contains facultative stem cells located in the small ductular segments (Hering canals) that connect hepatocytes with the ducts of the biliary tree. These cells appear capable, at least under certain conditions, of functioning as bipotential progenitors and to give rise to normal or transformed hepatocytes. It is a matter of debate whether the term stem cell is entirely appropriate because such cells may be part of a well-defined ductular segment.