Application of Fah knockout mice in the hepatocyte transplantation and the pathological changes / 中国药科大学学报

ABSTRACT

Aim: To investigate the pathological changes in NTBC[2-(2-nitro-4-trifluoro-methyl-benzoyl) -1,3 cy-clohexanedione]-induced hepatic injury in mice and in the repopulation of adult hepatocytes in Fah~(-/-) mouse. Methods: Autogenous hepatic injuries in Fah~(-/-) mice were induced by the treatment of NTBC. Injection of hepatocytes obtained from wild-type mice to spleen were transplanted into the Fah~(-/-) mice. Then, changes to body weight and the likelihood of the transplanted Fah~(-/-) mice, and hepatic immunohistochemistry were ob-served. In addition, pathological changes to liver damage induced by NTBC treatment were analyzed under HE-staining microscopy and electron microscopy. Results: The surviving Fah~(-/-) mice subjected to hepatocyte trans-plantation were found to be healthy and in stable body weight. liver repopulation reached to 90% in the 8th week. Repopulating hepatocytes caused no alteration to histological structure of the recipient liver, and subacute hepatic injury occurred in the Fah~(-/-) mice after NTBC treatment. Electronic microscopy observations indicated that necrosis in the hepatocytes occurred at early stage and that apoptosis gradually appeared. It was also shown both necrosis and apoptosis co-existed in the same samples of interest at the following stages of the induced liver injury. Conclusion: Transplanted hepatocytes proliferated in Fah~(-/-) mice allow 90% of the hepatocytic repopula- tion. Repopulation renders normal hepatic function and structure in the recipient Fah~(-/-) mice, as a model of liver repopulation, could be applicable in study of stem cell derived hepatic cells in transplantation assay.