Department of Military Cognitive and Stress Medicine, Institute of Military Cognitive and Brain Sciences, Academy of Military Sciences, Beijing, 100850, China.
Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Academy of Military Sciences, Beijing, 100850, China.
Stem Cell Res Ther. 2021 Feb 15;12(1):133. doi: 10.1186/s13287-021-02205-z.
The purpose of this study was to investigate the therapeutic effects of genetically modified mesenchymal stem cells (MSCs) in the treatment of type 2 diabetes mellitus (T2DM) in order to identify a new method for treating diabetes that differs from traditional medicine and to provide a new means by which to fundamentally improve or treat diabetes.
MSCs derived from adipose tissue were modified to overexpress FGF21 and GLP1, which was achieved through lentiviral particle transduction. The cells were transplanted into BKS.Cg-Dock7m+/+Leprdb/Nju mice (T2DM mouse model). Injections of physiological saline (0.1 mL) and liraglutide (0.5 mg/kg) were used as negative and positive controls, respectively. ELISA or Western blotting was used for protein analysis, and quantitative real-time PCR was used for gene expression analysis.
Genetic modification had no effects on the morphology, differentiation ability, or immunophenotype of MSCs. Moreover, MSC-FGF21+GLP1 cells exhibited significantly increased secretion of FGF21 and GLP1. In the T2DM mouse model, the transplantation of MSC-FGF21+GLP1 cells ameliorated the changes in blood glucose and weight, promoted the secretion of insulin, enhanced the recovery of liver structures, and improved the profiles of lipids. Moreover, FGF21 and GLP1 exerted synergistic effects in the regulation of glucolipid metabolism by controlling the expression of insulin, srebp1, and srebp2.
Stem cell treatment based on MSCs modified to overexpress the FGF21 and GLP1 genes is an effective approach for the treatment of T2DM.
本研究旨在探讨基因修饰间充质干细胞（MSCs）治疗 2 型糖尿病（T2DM）的疗效，以期为糖尿病的治疗提供一种有别于传统医学的新方法，并为从根本上改善或治疗糖尿病提供新手段。
通过慢病毒颗粒转导，将脂肪组织来源的 MSCs 修饰为过表达 FGF21 和 GLP1。将细胞移植到 BKS.Cg-Dock7m+/+Leprdb/Nju 小鼠（T2DM 小鼠模型）中。生理盐水（0.1ml）和利拉鲁肽（0.5mg/kg）注射分别作为阴性和阳性对照。采用 ELISA 或 Western blot 进行蛋白分析，采用定量实时 PCR 进行基因表达分析。
基因修饰对 MSCs 的形态、分化能力和免疫表型没有影响。此外，MSC-FGF21+GLP1 细胞表现出明显增加的 FGF21 和 GLP1 分泌。在 T2DM 小鼠模型中，MSC-FGF21+GLP1 细胞的移植改善了血糖和体重的变化，促进了胰岛素的分泌，增强了肝脏结构的恢复，并改善了脂质谱。此外，FGF21 和 GLP1 通过控制胰岛素、srebp1 和 srebp2 的表达，在调节糖脂代谢方面发挥协同作用。
基于过表达 FGF21 和 GLP1 基因的 MSC 修饰的干细胞治疗是治疗 T2DM 的有效方法。
