Liver stem cells: A potential source of hepatocytes for the treatment of human liver disease

Severe liver injury often leads to the proliferation of oval cells, which differentiate along hepatocytic and biliary lineages. Because oval cells proliferate only when hepatocyte replication is impaired, they are considered to be the progeny of facultative liver stem cells (FLSCs). Identification and isolation of FLSCs has been hampered by the lack of markers that delineate these bipotential progenitors. We hypothesized that transition ductal cells are FLSCs because they are located in a unique anatomical niche sharing tight junctions with a neighboring hepatocyte and another terminal ductular cell. Alternatively, it has been proposed recently that bone marrow-derived stem cells are FLSCs since these cells differentiate along the hepatic lineage following colonization of the liver. The intent of this review is to provide insight into the nature and origin of liver stem cells and to explore the possibility that stem cell technology may lead to the development of clinical modalities for the treatment of human liver disease.