NOD小鼠体内利用生物支架负载免疫抑制因子及鼠骨髓间充质干细胞治疗糖尿病的研究

1型糖尿病（T1DM）是由淋巴细胞介导的以胰岛B细胞特异性损伤导致胰岛素生成绝对缺乏为特征的一种自身免疫性疾病，T细胞特异性识别抗原肽/MHC分子复合物(pMHC)后，由锌转运体8（ZnT8）介导的胰岛B细胞损伤是发病的重要环节。目前，新型载体负载同体干细胞来源的胰岛样细胞皮下植入逆转糖尿病仍然是当前研究难点之一，并且传统三维支架在促进干细胞诱导分化、诱导T1DM机体内自身反应性T细胞异常活化两方面仍有待进一步研究。本研究拟通过聚多巴胺嫁接技术使ZnT8表位/HLA-A二聚体和静电纺丝支架结合，并保留二聚体结构活性。一方面通过二聚体的释放诱导自发性T1DM动物模型NOD小鼠的免疫耐受；另一方面释放抗体后的支架，为BMSCs胰岛样细胞提供固相载体，最终实现生物支架的免疫调节治疗NOD小鼠糖尿病和诱导BMSCs胰岛样分化的双重功能。

Type 1 diabetes(T1DM) is an autoimmune disease mediated by lymphocytes and characterized by absolute insulin deficiency caused by the specific destruction of pancreatic islet B cells. Zinc transporter 8 (ZnT8) is the core antigen that causes autoimmune attack in patients with T1DM. Previous studies have shown that ZnT8/HLA dimer can induce the immune tolerance of T1DM by binding and blocking antigen-specific T cells, while cannot directly improve the body's insulin level. In our previous study, we has constructed BMSCs electrospinning composite inducing factor biological scaffold system, which has proved to be able to provide islet like seed cells. The aim of this project is to combine the seed cell scaffolds system with the immune tolerance technique to observe its insulin secretion function and its influence on the immune response of islet B cells, so as to obtain a long-term effective treatment scheme for normal type 1 diabetes model, NOD mice.