Fetal liver cell transplantation as a potential alternative to whole liver transplantation?

Because organ shortage is the fundamental limitation of whole liver transplantation, novel therapeutic options, especially the possibility of restoring liver function through cell transplantation, are urgently needed to treat end-stage liver diseases. Groundbreaking in vivo studies have shown that transplanted hepatocytes are capable of repopulating the rodent liver. The two best studied models are the urokinase plasminogen activator (uPA) transgenic mouse and the fumarylacetoacetate hydrolase (FAH)-deficient mouse, in which genetic modifications of the recipient liver provide a tissue environment in which there is extensive liver injury and selection pressure favoring the proliferation and survival of transplanted hepatocytes. Because transplanted hepatocytes do not significantly repopulate the (near-)normal liver, attention has been focused on finding alternative cell types, such as stem or progenitor cells, that have a higher proliferative potential than hepatocytes. Several sources of stem cells or stem-like cells have been identified and their potential to repopulate the recipient liver has been evaluated in certain liver injury models. However, rat fetal liver stem/progenitor cells (FLSPCs) are the only cells identified to date that can effectively repopulate the (near-)normal liver, are morphologically and functionally fully integrated into the recipient liver, and remain viable long-term. Even though primary human fetal liver cells are not likely to be routinely used for clinical liver cell repopulation in the future, using or engineering candidate cells exhibiting the characteristics of FLSPCs suggests a new direction in developing cell transplantation strategies for therapeutic liver replacement. This review will give a brief overview concerning the existing animal models and cell sources that have been used to restore normal liver structure and function, and will focus specifically on the potential of FLSPCs to repopulate the liver.