Limited contribution of cells of intact extrahepatic tissue origin to hepatocyte regeneration in transplanted rat liver

BACKGROUND. It is now well established that various adult somatic tissues harbor multipotent stem cells that can differentiate into a broad variety of cell types of all three germ layer origins. It remains controversial, however, whether they are a reservoir of cells utilized for emergent tissue repair or simply a vestige of evolution and, if the former is the case, to what extent they can potentially contribute to reconstitution of a specific organ. To get an insight in such a direction, we examined the extent of contribution of naive intact cells of extrahepatic origin to hepatocyte reconstitution in the transplanted liver with or without injury in the rat. METHODS. Liver from wild-type donor rats was transplanted to green fluorescent protein (GFP)-transgenic rats, and GFP-positive hepatocytes were examined with or without liver injury. RESULTS. The proportion of GFP-positive hepatocytes in the transplanted noninjured liver linearly increased by 0.0048% per week, that is, approximately 5×10 hepatocytes of extrahepatic origin were generated per day. Liver injury induced by treatment with 2-acetylaminofluorene and CCl4 or the additional application of hepatocyte growth factor did not further increase the percentage of GFP-positive hepatocytes. CONCLUSION. The present results indicate that cells derived from nonmanipulated extrahepatic tissues appreciably contribute, though limitedly, to hepatocyte reconstitution in the liver of the rat.