Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Cell Transplant. 2020 Jan-Dec;29:963689720904628. doi: 10.1177/0963689720904628.
Numerous studies have proposed the transplantation of mesenchymal stem cells (MSCs) in the treatment of typical type 2 diabetes mellitus (T2DM). We aimed to find a new strategy with MSC therapy at an early stage of T2DM to efficiently prevent the progressive deterioration of organic dysfunction. Using the high-fat-fed hyperinsulinemia rat model, we found that before the onset of typical T2DM, bone marrow-derived MSCs (BM-MSCs) significantly attenuated rising insulin with decline in glucose as well as restored lipometabolic disorder and liver dysfunction. BM-MSCs also favored the histological structure recovery and proliferative capacity of pancreatic islet cells. More importantly, BM-MSC administration successfully reversed the abnormal expression of insulin resistance-related proteins including GLUT4, phosphorylated insulin receptor substrate 1, and protein kinase Akt and proinflammatory cytokines IL-6 and TNFα in liver. These findings suggested that MSCs transplantation during hyperinsulinemia could prevent most potential risks of T2DM for patients.
许多研究提出了间充质干细胞(MSCs)移植在治疗典型 2 型糖尿病(T2DM)中的应用。我们旨在寻找一种新的策略,即在 T2DM 的早期阶段进行 MSC 治疗,以有效防止器官功能进行性恶化。使用高脂肪喂养的高胰岛素血症大鼠模型,我们发现,在典型 T2DM 发病前,骨髓来源的 MSCs(BM-MSCs)可显著减轻胰岛素升高和葡萄糖下降,并恢复脂代谢紊乱和肝功能障碍。BM-MSCs 还有利于胰岛细胞的组织学结构恢复和增殖能力。更重要的是,BM-MSC 给药成功地逆转了肝脏中胰岛素抵抗相关蛋白(包括 GLUT4、磷酸化胰岛素受体底物 1 和蛋白激酶 Akt 以及促炎细胞因子 IL-6 和 TNFα)的异常表达。这些发现表明,高胰岛素血症期间的 MSC 移植可以为患者预防 T2DM 的大多数潜在风险。