Effect of Differentiation of Bone Marrow Mesenchymal Stem Cells into Insulin-Producing Cells Via Transfection of Pdx-1,Ngn3 and MafA on Treatment of Type 1 Diabetic Rats
Objective Pancreatic duodenal homeobox 1(Pdx-1),neurogenin(Ngn3)and V-type tendon fibrosarcoma oncogene homolog A(MafA)co-transfected bone marrow mesenchymal stem cells(BMSCs)into insulin-producing cells(IPCs),transplanted to treat type 1 diabetic rats and observe its effect.Methods Pdx-1,Ngn3 and MafA trans-differentiation BMSCs into IPCs.There were 45 SD rat models of type 1 diabetes were prepared by Streptozotocin(STZ),then divided into BMSCs group(15 cases):subrenal capsule transplantation 2 × 106 BMSCs.IPCs group(15 cases):subrenal capsule transplantation 2 × 106 IPCs.Sham-operation group(15 cases):subrenal capsule transplantation equal saline.There were 15 healthy SD rats were taken as normal group:an equal amount of saline was injected subrenal capsule.Fast blood glucose and body weight were monitored at 0,7,14,21,and 28 days after transplantation of rats in each group.Peritoneal glucose tolerance test was performed on rats in each group after transplantation 21 day.Kidney tissues of each group were taken for immunohistochemistry after transplantation 28 day.Results The blood glucose levels of rats in the BMSCs and IPCs groups decreased over time.On day 21 of transplantation,the fasting blood glucose levels of rats in both groups were significantly lower than those on day 0 of transplantation,and both were lower than those in the sham-operation group during the same period(P＜0.05).On day 28 of transplantation,the fasting blood glucose levels of rats in the IPCs group were lower than those in the BMSCs group(P＜0.05).In diabetes rats,the area under the curve of intraperitoneal glucose tolerance test in IPCs group and BMSCs group was smaller than that in sham-operation group,and the area under the curve in IPCs group was the smallest(P＜0.05).Brown fluorescent insulin expression was observed in the renal tissue of rats in the BMSCs and IPCs groups,and the insulin fluorescence optical density in the IPCs group was higher than that in the BMSCs group(P＜0.05).Conclusion IPCS trans-differentiation from BMSCs by Pdx-1-Ngn3 and MafA induced can effectively reduce blood glucose in diabetic rats.
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