Transforming growth factor‐α accelerates hepatocyte repopulation after hepatocyte transplantation

Abstract

Although hepatocyte transplantation could be an alternative to orthotopic liver transplantation, many problems, such as rejection, location, required volume, and hepatocyte activity are currently unresolved. We previously demonstrated an anti-apoptotic effect in transgenic mice overexpressing transforming growth factor (TGF)-alpha. We herein present the details of a successful hepatocyte transplantation using TGF-alpha transgenic mice. We used transgenic (TG) mice which overexpressed human TGF-alpha controlled by the metallothionein promoter. Wild-type mice were used as the controls (WT). Parenchymal hepatocytes were isolated from an adult mouse by the modified in situ perfusion method. The proliferation and resistance to Fas-induced apoptosis were examined in vitro. In addition, we transplanted the parenchymal hepatocytes into the peritoneal cavity of the WT mice. The TG hepatocytes showed higher proliferative activity and more resistance to Fas-induced apoptosis in comparison to the WT hepatocytes. Moreover, an immunohistochemical analysis demonstrated that the transplanted TG hepatocytes increased more in size and showed a higher expression of CD31 and vascular endothelial growth factor in comparison to the WT hepatocytes. We also observed that albumin was expressed in equal amounts in both types of transplanted hepatocytes. Cell transplantation with TGF-alpha overexpressing hepatocytes could preserve hepatocyte function.