Studies On The Therapy Of End-stage Liver Disease By Bone Marrow Stem Cells Transplantation

Objective Donor organ shortage significantly hinders orthotopic liver transplantation therapy, the only effective treatment for chronic end-stage liver disease and acute liver failure. So cell transplantation as one of the strategies with potential for treatment of such liver disorders has been paid much attention to. This study is focus on whether the transplantation of MSCs as allograft could improve liver function and to clarify the distribution of these transplanted MSCs. On the basis of that, the purpose of this investigation is also to discuss the safety, feasiblity and validity of autologous bone marrow stem cells transplantation into patients'livers to treat hepatocirrhosis so as to provide a new therapeutic approach to treat end-stage liver disease.Methods First, the rat acute hepatic injury model was established by the use of 2-AAF. The homogeneous MSCs from male rats were transplanted into female rats'livers through portal vein, then the changes of serum ALB, ALT and AST were detected, furthermore, the distributions of transplanted MSCs were observed by means of fluorescence label, immunohistochemistry and nestal PCR. At same time, 201 hepatocirrhosis patients were collected. Autologous bone marrow stem cells transplantation was carried on 131 of these patients, their bone marrow were harvested and bone marrow stem cells were isolated by density grads centrifuge and then were applied to patients by intubatton through hepatic artery, the changes of serum ALB, CHE, PTA and TBil were detected, at the same time, the patients'symptoms, complications and prognosis were also observed.Results 2-AAF could induce diffuse hepatic injury. In rats that were pretreated with 2-AAF, serum ALB value was higher than that in control rats 3 weeks after transplantation. The distribution of transplanted bone marrow MSCs was as follows: 1 week after transplantation, DAPI positive cells dispersed in liver, lung and spleen. But positive cells only could be found in injured liver 3 weeks after transpalntation, these cells were in clusters and phenotypically resembled hepatocyte. SRY protein and gene could be detected...