Adult Liver Stem Cells

The definition of liver stem cells includes: cells responsible for normal tissue turnover; cells which give rise to regeneration after partial hepatectomy, cells responsible for progenitor-dependent regeneration, cells which produce in hepatocyte and bile duct epithelial phenotypes in vitro, and transplantable liver repopulating cells. This chapter discusses liver stem cells according to each of these definitions. The liver is known to have a very high capacity for regeneration. The original number of cells is restored within one week and the original tissue mass within two to three weeks. Liver size is also controlled by prevention of organ overgrowth. Hepatic overgrowth can be induced by a variety of compounds, such as hepatocyte growth factor or peroxisome proliferators. In mammals, the adult liver contains many different cell types of various embryological origins. The term liver or hepatic stem cell is used only for precursors of the two epithelial liver cell types, the hepatocytes and bile duct epithelial cells. Hepatocyte and bile duct stem cells are discussed here. The role of liver stem cells in regeneration has been controversial, but many of the apparent inconsistencies can be reconciled by considering the different definitions that have been used for these cells. Current evidence strongly suggests that different cell types and mechanisms are responsible for organ reconstitution, depending on the type of liver injury. Tissue replacement by endogenous cells (regeneration) must be distinguished from reconstitution by transplanted donor cells (repopulation).