ABSTRACT
Objective To evalute the feasibility of treatment for rabbit model with hepatic cirrhosis by transplantation of autologous bone marrow-derived stem cells via the hepatic artery and evaluate the effect of hepatocyte growth-promoting factors (pHGF) in the treatment of stem cells transplantation to liver cirrhosis.To provide empirical study foundation for future clinical application.Methods Chronic hepatic cirrhosis models of rabbits were developed by subcutaneous injection with 50% CCl4 0.2 ml/kg.Twenty-five model rabbits were randomly divided into three experimental groups,stem cells transplant group (10),stem ceils transplant + pHGF group (10) and control group (5).Autologous bone marrow was harvested from tibia of each rabbit,and stem cells were disassociated using density gradient centrifugation and transplanted into liver via the hepatic artery under fluoroscopic guidance.In the stem cells transplant + pHGF group,the hepatocyte growth-promoting factor was given via intravenous injection with 2 mg/kg every other day for 20 days.Liver function tests were monitored at 4,8,12 weeks intervals and histopathologic examinations were performed at 12 weeks following transplantation.The data were analyzed using analysis of variance Results Following transplantation of stem cells,the liver function of rabbits improved gradually.Twelve weeks after transplantation,the activity of ALT and AST decreased from (73.0±10,6)U/L and(152.4± 22.8) U/L to (48.0±1.0)U/L and(86.7±2.1)U/L respectively; and the level of ALB and PTA increased from (27.5 ±1.8)g/L and 28.3% to (33.2 +0.5)g/L and 44.1% respectively.The changes did not have statistically significant difference when compared to the control group(P >0.05).However,in the stern cellstransplant + pHGF group,the activity of ALT and AST decreased to (43.3±0.6)U/L and (78.7±4.0)U/L respectively and the level of ALB and PTA increased to (35.7 ±0.4)g/L and 50.5% respectively.The difference was statistically significant when compared to the control group(F=47.38,23.52,52.27,174.45,P < 0.05).In pathohistology,the degeneration and necrosis of hepatic cells and the degree of fibrous hyperplasia in stem cells transplant group were less obvious than that of the control group.Hepatic pseudo-lobules persisted.The improvement of liver architecture in the stem cells transplant + pHGF group was more evident than that in stem cells transplant only group.In addition,there were more hepatic CD34 <'+> cells within liver tissue in the stem cells trasplant group when compared to the control group,and the most hepatic CD34<'+> cells were seen in the stem cells transplant + pHGF group.Conclusion Autologous bone marrow stem cells transplanted via the hepatic artery for the rabbit hepatic cirrhosis model is an effective method to treat hepatic cirrhosis.The hepatoeyte growth-promoting factor can help to enhance the results of treatment.