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.

中文翻译：

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FGF21和GLP1修饰的间充质干细胞改善脂质代谢，同时降低2型糖尿病小鼠的血糖

这项研究的目的是调查基因修饰的间充质干细胞（MSCs）在治疗2型糖尿病（T2DM）中的治疗效果，从而确定一种不同于传统药物的新型治疗糖尿病的方法，并提供一种从根本上改善或治疗糖尿病的新方法。源自脂肪组织的MSCs经过修饰以过表达FGF21和GLP1，这是通过慢病毒颗粒转导实现的。将细胞移植到BKS.Cg-Dock7m + / + Leprdb / Nju小鼠（T2DM小鼠模型）中。生理盐水（0.1 mL）和利拉鲁肽（0.5 mg / kg）分别用作阴性和阳性对照。ELISA或Western blotting用于蛋白质分析，定量实时PCR用于基因表达分析。基因修饰对MSC的形态，分化能力或免疫表型没有影响。而且，MSC-FGF21 + GLP1细胞显示出FGF21和GLP1的分泌显着增加。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，并改善了脂质的分布。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中发挥协同作用。基于修饰过表达FGF21和GLP1基因的MSC的干细胞治疗是治疗T2DM的有效方法。MSC-FGF21 + GLP1细胞显示出FGF21和GLP1的分泌显着增加。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，并改善了脂质的分布。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中发挥协同作用。基于修饰过表达FGF21和GLP1基因的MSC的干细胞治疗是治疗T2DM的有效方法。MSC-FGF21 + GLP1细胞显示出FGF21和GLP1的分泌显着增加。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，并改善了脂质的分布。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中发挥协同作用。基于修饰过表达FGF21和GLP1基因的MSC的干细胞治疗是治疗T2DM的有效方法。并改善了脂质的分布。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中发挥协同作用。基于修饰过表达FGF21和GLP1基因的MSC的干细胞治疗是治疗T2DM的有效方法。并改善了脂质的分布。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中发挥协同作用。基于修饰过表达FGF21和GLP1基因的MSC的干细胞治疗是治疗T2DM的有效方法。