The Effects Of Marrow Mesenchymal Stem Cells On Xenogeneic Islet Cell Transplantaiton

Previous studies have confirmed that Marrow mesenchymal stem cells(MSC)can suppress immune rejection in the heart and liver allograft rejection and extend the graft survival time. There are few reports about MSC in the induction of xenogeneic transplant immune tolerance. Xenogeneic islet cell transplantation is potential to cure Type I diabetes mellitus (IDDM) with its advantages of sufficient source of donor, but the xenogeneic rejection limited its wide application. It is crucial to solve the problem that how to induce immune tolerance of xenogeneic pancreatic islet cell transplantation. T cell vaccination is a potential method of inducing transplantation immune tolerance. In this study, donor antigen specific MSC was used to immunize recipients before transplantation and the blood glucose and body weight changes were monitored after xenogeneic islet cell transplant.Objectives : To explore the effects of Marrow mesenchymal stem cells vaccination on inducing xenogeneic islet transplant tolerance .Methods: Type 1 diabetes mice model were made by injecting streptozotocin intravenously. Wistar rat pancreas.was harvested and islet cells were isolated from Wistar rat pancreas using the protocol of enzyme digestion and density gradient centrifugation . It is certain to maintain aseptic technique in the whole process. TypeⅠiabetes mice were randomly divided into three groups, Group A :Diabetic mice with no transplantation and no TCV, Group B(experimental group): Islet cell transplantation+MSC, Group C (control group):Islet cell transplantation . Balb/c mice as recipients were immunized with MSC on the time points of d-14 , d-7 and d-1; Islet cells were transplanted into immunized Balb/c mice at the density of 1500IEQ/one by the way of portal vein injection.Recipient,s blood glucose was monitored everyday and body weight was recorded weekly after transplantation.Results: It is successful IDDM models when blood glucose levels of Balb/c mice rose to 16.7mmol / l and kept stable through the 5th day. Islet cells were stained with DTZ to comfirm the Islet cells, production reached (3568±375) IEQ / pancreas, the purity reached 70%-80%, AO-PI staining islet cells, live rate reached 80%-90% .The lever of blood glucose in mice before islet cell transplantation during the observation period: the diabetic mice group(22.3±1.66)mmol /l,the control group (21.6±1.73)mmol/l,the experimental group(23.3±1.29)mmol/l.Islet cell transplantation:The non-transplanted group showed a sustained high blood glucose levels,The blood glucose levels of the transplanted mice began to decline after 24h. The blood glucose value of the control group was(11.3±0.91)mmol/l in the3th days after transplantation and reached the lowest value (9.6±1.47) mmol/l in 4th days after transplantation. The value reached(18.9±1.62)mmol/l in the 8th days after plateau of 2 days.The blood glucose value of the experimental group was(11.6±1.77)mmol/l in the3th days after transplantation and reached the lowest value (6.8±1.56) mmol / l in 6th days after transplantation.The value reached(19.3±1.34))mmol/l in the 24th days after plateau of 14 days.The changes in body weight of each group is similar to each other before islet cell transplantation. experimental group and control group body weight increased gradually after normal blood glucose levels, control group began to decline in the d10 after transplantation. The experimental group continued to increased to d26 after transplantation.Conclusion: marrow mesenchymal stem cells can significantly prolong the survival time of xenogeneic pancreatic islet grafts ; marrow mesenchymal stem cells is a potential approach to to induce xenogeneic islet transplant tolerance .