Stem Cells of the Liver: Basic Science and Clinical Applications

The liver normally exhibits a very low level of cell turnover, is capable of regeneration to replace hepatocyte loss very precisely from residual parenchymal tissue. 1 More significantly from a human disease standpoint, longstanding iterative injury (eg chronic viral hepatitis), often associated with hepatocyte replicative senescence, activates a facultative (potential) stem cell compartment within the intrahepatic biliary tree, which can generate cords of bi-potential transit amplifying cells (called oval cells in rodents and hepatic progenitor cells [HPCs] in man), that ultimately differentiate into hepatocytes and biliary epithelial cells. Bone marrow cells (BMCs) may also contribute to parenchymal replacement, though this is likely to be a trivial event within the body. 2 On the other hand, cellular therapies for intractable liver disease have tended to focus on BMCs, perhaps because they have a role in extracellular matrix degradation. This chapter outlines the regenerative capacity of the liver, illustrates principles underlying successful cell transplantation and discusses recent advances in cell therapies for metabolic and fibrogenic liver diseases.