This difference might be attributable to the different properties of human and rat MSCs when human MSCs are xenotransplanted and when rat MSCs undergo syngeneic transplantation. Notably, the liver from GFP-Tg Lewis rats can survive in wildtype syngeneic rats despite vigorous rejection of transplanted hepatocytes in this situation. Typically a liver graft is rejected approximately 10 days after allogeneic transplantation when there is a severe rejection reaction. A shorter treatment with a low dose of tacrolimus resulted in the liver graft surviving in allogeneic Ro 15-4513 recipients despite the MHC barrier. Generally, the same amount of immunosuppressant treatment is insufficient to prevent graft loss of other organs such as heart, kidney, and skin, and the mechanism of liver graft survival after shorter and smaller doses of immunosuppressant includes the release of non-specific immune modulators from the liver graft and the functional role of non-parenchymal cells in the graft. In contrast, the majority of the transplanted hepatocytes are eliminated from the host liver within the first few days by a nonspecific immune response that leads to foreign antigen presentation and acceleration of the immune reaction. Identification of the major mechanism determining the tolerance of liver grafts and the rejection of hepatocytes is of major importance. Modulation of the factors involved would be beneficial for the control of immune response after liver and hepatocyte transplantation, as well as other organ transplantation. Very few large, GFP-positive polygonal cells were residing in the hepatic cords of retrorsine-pretreated livers after bone marrow transplantation but without hepatocyte transplantation, as shown in Experiment 4. Our previous study using transplantation of wildtype retrorsine-pretreated liver into GFP-Tg syngeneic rats identified a similar group of cells that represented less than 0.02% of total hepatocytes at eight weeks after liver transplantation. This population of hepatocytes expressed GFP, albumin, and CYP1A2, suggesting that they were functional hepatocytes. Majorities of these abnormally large, hepatocyte-like cells resided in hepatic cords solitarily despite the expression of Ki67. We also identified a group of small cells that were capable of vigorous proliferation in the same liver Radicicol samples. Therefore, it is plausible that the abnormally large GFP-positive polygonal cells are derived from the fusion of endogenous hepatocytes exposed to retrorsine and bone marrow cells, whereas the very small polygonal cells are derived by transdifferentiation of bone marrow cells. Thus, we agree with the model proposed by Masson et al. that cell fusion and cell transdifferentiation depends upon the liver environment. A comprehensive study using sex-mismatched liver or bone marrow transplantation is necessary to clarify this issue. In this experiment, we have demonstrated that hepatocytes from GFP-Tg Lewis rats are not able to survive long-term in the syngeneic wild-type Lewis rat liver. Liver is not an immuneprivileged site for hepatocyte transplantation, and multiple factors determine the death or survival of transplanted hepatocytes.