Liver repopulation by transplanted hepatocytes in a rat model of acute liver failure induced by carbon tetrachloride and a partial hepatectomy
Satoshi Mochizuki, Yujo Kawashita, Susumu Eguchi, Mitsuhisa Takatsuki, Kosho Yamanouchi, Hirotaka Tokai, Masaaki Hidaka, Akihiko Soyama, Shigeki Nagayoshi, Takashi Kanematsu
Ann Transplant 2010; 15(4): 49-55
Available online: 2010-12-22
Background: Although hepatocyte transplantation holds great promise, most of the transplanted hepatocytes fail to proliferate in the liver without any manipulation of the host. Previous studies have shown that the replacement of the host liver cells with transplanted hepatocytes, called “liver repopulation”, requires a combination of proliferative stimuli to the transplanted hepatocytes and suppression of the host hepatocytes. This study explored whether liver repopulation could be achieved by hepatocyte transplantation in a chemically and surgically induced-liver failure model in the rat.
Material/Methods: Dipeptidyl peptidase IV-positive (DPPIV +) Fisher rats were used as donor and syngeneic DPPIV-deficient (DPPIV –) rats served as recipient. The recipient rats were treated with carbon tetrachloride (CCl4) for 4 weeks followed by a 68% partial hepatectomy (PH) and transplantation of the hepatocytes (HT). Five groups were established based on the influence of specific factors including CCl4, PH, and HT. The liver regeneration rates were evaluated by the liver weight/body weight (LW/BW) ratio. The liver repopulation rates were determined by the formula; (DPPIV+ cell counts/all cell counts) ×100%.
Results: The liver regeneration rates were 3.5 and 2.6 in the rats with CCl4+PH, and PH alone, respectively (P<0.01). In the rats with CCl4+PH, DPPIV positive cell clusters appeared in the host liver parenchyma 7 days after HT (day 7), exhibiting continuous proliferation up to day 28 (The liver repopulation rates were 1.1% and 13.4%, respectively, p<0.05).
Conclusions: Liver repopulation by hepatocyte transplantation was therefore found to be possible in partially hepatectomized rats under the continuous exposure to regulated doses of CCl4.
Keywords: hepatocyte transplantation, Carbon Tetrachloride, CCl4 , liver repopulation