Hepatic Stem Cells in Liver Regeneration

The concept that the liver contains epithelial cells that share some of the major properties of stem cells of the well-characterized, stem cell-fed lineages found in bone marrow, intestinal epithelium, and epidermis is now well supported. Nevertheless, the population dynamics of the major types of liver epithelial cells, hepatocytes, and bile epithelia display a striking difference from the population dynamics of the classic stem cell systems. The focus of this review is on recent studies of the activation and expansion of liver stem cells in vivo and the role these cells may play in regeneration of the liver. The requirement for a selective and sustained expression of growth factors during the early stages of stem cell activation is highlighted. In addition, results are presented supporting the hypothesis that after loss of liver mass, both the quiescent stem cells as well as the residual differentiated hepatocytes and bile duct epithelial cells are activated to proliferate. However, significant contribution of the stem cells to the regeneration process only occurs under circumstances in which the residual differentiated cells are functionally compromised and/or cannot proliferate.