Liver repopulation by cell transplantation and the role of stem cells in liver biology

The major impetus for trying to reconstitute the liver by cell transplantation is based on the very high regenerative capacity of this organ. Substantial progress has been made defining the cell types that can repopulate the liver and restore function, and the host liver conditions under which effective repopulation can be achieved. Hepatocyte transplantation has been shown to be therapeutic in animal models of acute liver failure and limited human clinical studies have been promising. Liver regeneration is a highly organized, complex process involving growth factors and cytokines, transcription factors, cell signaling pathways, and expression of cell cycle regulatory genes. The phenomenon of plasticity and transdifferentiation between ductal epithelial cells and hepatocytes has become more appreciated and experimentally proven. Many questions regarding the basic biology of stem cells in the liver remain unresolved, including the all-important question of whether hepatic stem cells exist at all in the adult liver.