The Experimental Study On Therapeutic Effect Of Acute Liver Injury By Transplanting Allogeneic Bone Marrow Stromal Cells Into Liver

BACKGROUND/AIMS Recent reports have shown the capacity of bone marrow stromal cells(BMSCs)to differentiate into hepatocytes in vitro and in vivo.BMSCs administration could repair injured liver through reducing inflammation,collagen deposition,and remodeling. These results provide a clue that the syngenic transplantation of BMSCs is a promising treatment for liver disease.Pluripotent BMSCs can differentiate into hepatocytes,but few reports address the therapeutic effect of transplanting these stem cells into damaged liver in vivo.The aim of this study was to investigate the therapeutic effect of infusion of BMSCs on acute hepatic injury(AHI)rabbits induced by D-galactosamine.METHODS BMSCs were derived from bone marrow obtained from femoral and tibial bones of male albino rabbits.BMSCs were separated,grown,and propagated in culture for 3 weeks and were characterized morphologically.They were then infused directly into livers of syngenic male rabbits that received D-galactosamine injection to induce liver injury.AHI rabbits(n=58)were divided into 2 random groups on the 24th hour of D-GalN:D-GalN/BMSCs(n=24),to infuse 5 ml(about 2×10~7)BMSCs directly as treated group.D-GalN/D-hanks(n =34),to infuse the same dose of D-hanks as control.Then behavioral changes:of rabbits were monitored everyday.The survival rates were observed and liver functions(ALT,AST,ALB and TBIL)were estimated for all groups.After 1-4 wk of BMSCs administration,all rabbits were killed with different time(1 wk,2 wk,4 wk)respectively and histopathological changes and degrees of necrosis in the hepatic tissues were assessed also.Two histopathologists blinded to treated group and each other's results measured liver histopathological scores.All data should be analyzed by SPSS 13.0.RESULTS Survival rate of D-GalN/BMSCs Group 1 weeks later was higher than that of control(95.8%vs 70.6%,P＜0.05).On the other hand,the survival rate of D-GalN/BMSCs Group 2 weeks later was not improved significantly as compared with that of control(100%vs 82.4%,P＞0.05).With regard to liver function,there was also a significant improvement and elevation of Serum albumin in the D-GalN/BMSCs group compared to the D-GalN/D-hanks group (p＜0.05).As regard to the liver enzyme ALT and AST,there was also a significant decrease of its level in the D-GalN/BMSCs group compared to the D-GalN/D-hanks group(p＜0.05).However,the level of TBIL of 2 groups was statistically nonsignificant(p＞0.05).Results of the histopathological scores showed that BMSCs have a significant anti-injurious activities as evidenced by the significant decrease in liver necrosis as well as the stimulate hepatocytes proliferation in the D-GalN/BMSCs group compared to the D-GalN/D-hanks group(p＜0.001).CONCLUSIONS The transplantation of BMSCs effectively contribute to the repair of the severely acute liver injury in D-GalN-induced rabbits.Injection of BMSCs directly into the liver is the simple route of administration in experimental model.