Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
J Cell Physiol. 2019 Nov;234(11):20310-20321. doi: 10.1002/jcp.28631. Epub 2019 Apr 17.
Type 1 diabetes, has been recognized as an autoimmune disease. Like other immunological conditions, regulation of immune response is a key strategy to control the autoimmunity in diabetic patients. Mesenchymal stem cells have been shown to have a distinct potential in modulating the immune reactions. However, treatment with stem cells is combined with concerns about safety issues. To overcome these concerns, in this study, we have utilized the regenerative potential of exosomes isolated from menstrual blood-derived mesenchymal stem cells to restore the β-cell mass and insulin production in type 1 diabetes. Exosomes are nanovesicles containing various cargos involved in cellular communications. Streptozotocin was used to induce islet destruction and diabetes in male Wistar rats. Then, exosomes were intravenously injected into animals at different time points and in a single or repeated therapeutic doses. After about 6 weeks, animals were euthanized and the pancreas was analyzed for the presence of the regenerated β islets as well as the insulin secretion. The non-fasting blood glucose and the serum insulin level were also monitored during the study. Our results represented that menstrual blood-derived mesenchymal stem cell-derived exosomes enhance the β-cell mass and insulin production in the pancreas of diabetic animals that received repeated doses of exosomes. Immunohistochemistry analysis also confirmed the presence of insulin in the islets of treated animals. Further investigations proposed that exosomes induce the islet regeneration through pancreatic and duodenal homeobox 1 pathway. The exosome tracking also revealed the homing of injected exosomes to the pancreas.
1 型糖尿病已被认为是一种自身免疫性疾病。与其他免疫状况一样，调节免疫反应是控制糖尿病患者自身免疫的关键策略。间充质干细胞在调节免疫反应方面具有明显的潜力。然而，干细胞治疗与安全性问题有关。为了克服这些担忧，在这项研究中，我们利用从月经血来源的间充质干细胞中分离的外泌体的再生潜力来恢复 1 型糖尿病中的β细胞质量和胰岛素产生。外泌体是含有参与细胞通讯的各种 cargo 的纳米囊泡。链脲佐菌素用于诱导胰岛破坏和糖尿病雄性 Wistar 大鼠。然后，在不同时间点以单次或重复治疗剂量将外泌体静脉注射到动物体内。大约 6 周后，处死动物，分析胰腺中是否存在再生的β胰岛以及胰岛素分泌情况。在研究过程中还监测了非禁食血糖和血清胰岛素水平。我们的结果表明，月经血来源的间充质干细胞衍生的外泌体增强了接受重复剂量外泌体的糖尿病动物的β细胞质量和胰岛素产生。免疫组织化学分析也证实了治疗动物胰岛中存在胰岛素。进一步的研究表明，外泌体通过胰腺和十二指肠同源盒 1 途径诱导胰岛再生。外泌体追踪还揭示了注射的外泌体向胰腺的归巢。
