Intrasplenic Transplantation Of Hepatocyte-like Cells Induced By BMP-4 To Rescue Acute Liver Failure In SD Rats

Objective:To investigate the treatment effect of transplanted hepatocyte-like cells induced by BMP-4 in the rats acute liver failure through spleen.Methods:Stimulated the prolification of liver stem cells, isolated and cultured primary hepatic oval cells. Design adenovirus vector,amplificate hepatic oval cells in vitro. Identification of the differentiated cells and primary hepatic oval cells by cell immunofluorescence in vitro.4x10′cells diluted by lml saline or 1ml saline were injected into the spleen of acute liver failure rats which were induced by CCl4. Recording the survival rates of the rats after surgery,drawing blood from tail vein during 2nd,5th,7th, then sends to test liver function, take the livers to histopathological and immunofluo-rescence examination.Results:OV6 as the hepatic progenitor marker,were expressed in primary hepatic oval cells, Alb and CK19 were negative in this cells.The differentiated HOC induced by BMP-4 express GFP 24h after transfection,and express the hepatocyte marker Alb 18 days after cultured in vitro.The survival rates,liver functions and restore effect of the liver in Ad-BMP-4 group are better than the control group (P<0.05). Tissue immunofluorescence showed that the total number of the GFP-positive cells and proliferation phenomenons in the experimental group was significantly better than the control group.Conclusion:Hepatic oval cells can be differentiated into hepatocyte-like cells induced by BMP-4. Transplantation of hepatic oval cells deprived hepatocyte-like cells through the spleen, hepatoctye-like cells may replace part of liver function and secretion of soluble cytokines to stimulate hepatocytes proliferation, thereby enhancing the CCL4-induced acute liver failure survival rates and accelerate the repair of liver injury.