间充质干细胞与未成熟树突细胞联合胰岛细胞移植治疗小鼠糖尿病

Co-Transplantation of Islets with Mesenchymal Stem Cells and Immature Dendritic Cells in the Treatment of Mouse Diabetes

为建立一种有效的胰岛移植免疫耐受的新方案,利用流式细胞术鉴定未成熟树突细胞(immature dendritic cells,im DCs),成骨诱导鉴定间充质干细胞(mesenchymal stem cells,MSCs),双硫腙(Dithizone,DTZ)染色鉴定胰岛细胞.胰岛细胞与间充质干细胞联合移植治疗小鼠糖尿病,测定移植后糖尿病小鼠血糖及糖化血红蛋白变化,结果发现200个胰岛细胞与2×10~5个未成熟树突细胞共同移植虽然未能显著延长移植物的存活时间(7±2.65d),但能显著降低糖尿病小鼠血糖水平;200个胰岛细胞与2×10~5个间充质干细胞共移植,可使血糖下降到较低水平,并维持移植物存活时间达8±2.31天;200个胰岛细胞与2×10~5个间充质干细胞及2×10~5个未成熟树突细胞共同移植于糖尿病小鼠,可使糖尿病鼠血糖下降并显著延长移植物的存活时间(12.6±3.48 d).结果说明联合移植在一定程度上可延长移植物的存活时间并使血糖维持在较低的水平,有效控制糖化血红蛋白浓度,较单独移植胰岛细胞治疗小鼠糖尿病有积极的作用.

To establish an effective plan for immune tolerance of islets transplantation,immature dendritic cells( im DCs) were identified by flow cytometry( FCM). Mesenchymal stem cells( MSCs) were incubated to differentiate into osteoblasts and islets were identified with dithizone( DTZ) staining method. From the results of three co-transplantation groups,it was found that transplantation did not significantly prolong graft survival( 7 ± 2. 65d),but remarkedly decreased blood glucose and glycosylated hemoglobin concentration in the diabetes of mouse by co-transplantation of 200 islets and 2 × 10~5 im DCs. Co-transplantation of 200 islets with 2 × 10~5 MSCs could significantly decrease blood glucose level and prolong graft survival for 8 ± 2. 31 days. Transplantation of 200 islets with2 × 10~5 MSCs and 2 × 10~5 im DCs could not only restore normal blood glucose level,but also significantly prolong graft survival for 12. 6 ± 3. 48 days. This result indicates that co-transplantation of islets with im DCs or MSCs can promote graft survival and reverse blood glucose level,and at the meanwhile effectively control the glycosylated hemoglobin concentration as well,which is better than islets transplantation alone.