Sun Yun, Mao Qianyun, Shen Chao, Wang Chen, Jia Weiping
Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, People's Republic of China.
Diabetes Metab Syndr Obes. 2019 Oct 8;12:2053-2064. doi: 10.2147/DMSO.S213400. eCollection 2019.
Exosomes are small nanoscale vesicles secreted from cells. Exosome-based therapeutic approaches have been evaluated in treating ischemic diseases. In the present study, we explored the effect of exosomes on streptozotozin (STZ)-induced diabetic mouse and its underlying mechanisms.
Exosomes were isolated from MIN6 cells. Transmission electron microscopy, dynamic light scattering and Western blot were used to identify the exosomes. STZ was used to establish diabetic or abnormal glucose tolerance mouse model. Histology study and flow cytometry were applied to detect the changes in immune responses.
Transplantation of the exosomes into diabetic mice resulted in a longer median survival time compared with the untreated diabetic mice (<0.01). Transplantation of the exosomes improved glucose tolerance, increased insulin content and preserved the architectures of islets in mice with abnormal glucose tolerance. Moreover, exosome treatment enhanced the expression of CD31, a marker of endothelial cells, and tended to reduce macrophage infiltration in islets of STZ-treated mice.
Exosomes derived from β-cells play a role in preserving pancreatic islet architecture and its function, and in inducing islet angiogenesis, which implicates that exosome treatment could be a novel therapeutic strategy for diabetes.
外泌体是细胞分泌的纳米级小囊泡。基于外泌体的治疗方法已在缺血性疾病治疗中得到评估。在本研究中,我们探讨了外泌体对链脲佐菌素(STZ)诱导的糖尿病小鼠的影响及其潜在机制。
从MIN6细胞中分离出外泌体。采用透射电子显微镜、动态光散射和蛋白质印迹法对外泌体进行鉴定。使用STZ建立糖尿病或葡萄糖耐量异常小鼠模型。应用组织学研究和流式细胞术检测免疫反应的变化。
与未治疗的糖尿病小鼠相比,将外泌体移植到糖尿病小鼠体内可使中位生存时间延长(<0.01)。外泌体移植改善了葡萄糖耐量,增加了胰岛素含量,并保留了葡萄糖耐量异常小鼠胰岛的结构。此外,外泌体治疗增强了内皮细胞标志物CD31的表达,并倾向于减少STZ处理小鼠胰岛中的巨噬细胞浸润。
β细胞来源的外泌体在维持胰岛结构及其功能以及诱导胰岛血管生成方面发挥作用,这表明外泌体治疗可能是一种治疗糖尿病的新策略。