Rat Liver Repopulation by Transplanted Late Gestation Fetal Hepatocytes

Hepatocyte transplantation has the potential to be an effective therapy for liver failure. However, the application of this therapy has been hampered by identification of an appropriate cell population and limited understanding of the factors accounting for the ability of cells to repopulate injured liver. Late gestation (E19) fetal hepatocyte proliferation in the rat is mitogen-independent in vivo and in vitro. Fetal hepatocytes also differ from adult hepatocytes with regard to ribosome biogenesis, translation control, gene expression and cell cycle regulation. Our current studies are based on the hypothesis that histone posttranslational modifications (PTMs) acting through effects on chromatin structure account for the fetal hepatocyte signaling phenotype and that this phenotype will result in a selective growth advantage for fetal cells in the injured adult liver microenvironment. Late gestation fetal hepatocytes were isolated using antibodies against hepatic and ductal cell surface markers. The engraf...