Liver Regeneration and α-Fetoprotein Messenger RNA Expression in the Retrorsine Model for Hepatocyte Transplantation

摘要: Recently, we described a new model for hepatocyte transplantation with nearly total replacement of the liver by exogenous hepatocytes (E. Laconi et al., Am. J. Pallidi.. 753: 319-329, 1998). The is based on mitoinhibitory effect pyrrolizidine alkaloid reti-orsine hepa tocytes in resident while transplanted proliferate. In this study, exploit novel approach to address important and controversial issue whether hepatocytes, when proliferating extensively, undergo dedifferentiation give rise foci undifferentiated tocytes. Genetically marked (isolated from normal Dipeptidyl peptidase IV Fischer 344 rats) were delivered intraportally (2 x 10'' cells) into retrorsine-treated mutant rats conjunction partial hepatectomy. Transplanted detected histochemically or immunohistochemically, cell proliferation was studied situ hybridization histone-3 mRNA. Expression a-fetoprotein (AFP) mRNA, marker dedi fferentiation, also revealed hybridization. One day after hepatectomy transplantation, endogenous hepato cytes oval cells expanding expressed mRNA (cells had entered S phase); 2 days later, nonparenchymal Although ma jority did not divide became arrested as quiescent megalocytes, well newly formed small most probably derived progenitor cells, underwent extensive proliferation. After 7-14 days, stopped proliferating, but endog enous continued proliferate 1 month, forming dividing parenchyma! cells. many clusters phase (histone-3 positive), none AFP contrast, high expression observed