Abstract
ObjectiveThe 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.MethodsMSCs 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.ResultsGenetic 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.ConclusionStem cell treatment based on MSCs modified to overexpress the FGF21 and GLP1 genes is an effective approach for the treatment of T2DM.
Highlights
Diabetes mellitus (DM) is a complex metabolic disease characterized by chronic hyperglycemia, insulin resistance, and islet β-cell dysfunction [1,2,3]
Flow cytometry analysis showed that when the multiplicity of infection (MOI) was 40, the number of EGFP-positive cells was more than 95%, and the transfection efficiency was not significantly improved between MOIs 40 and 55 (Fig. 2c)
The differentiation ability and surface marker expression of Mesenchymal stem cell (MSC) transfected with Fibroblast growth factor 21 (FGF21) + glucagon-like polypeptide 1 (GLP1) were detected
Summary
Diabetes mellitus (DM) is a complex metabolic disease characterized by chronic hyperglycemia, insulin resistance, and islet β-cell dysfunction [1,2,3]. There are millions of people in the world with diabetes, and the risk of developing diabetes in the future is very high [4]. According to a report published in Lancet Diabetes and Endocrinology, the number of people with T2DM will increase from 406 million in 2018 to 511 million by 2030, and this increase will be the result of the continuous increase in global obesity [5]. The treatment of diabetes is a long-term process. The long-term use of various chemicals has many limitations and leads to adverse effects and even serious complications, such as hypoglycemia and lactic acidosis. It is not easy for patients to adhere to this treatment, which requires strict control of the administration time and dose; otherwise, hypoglycemia can occur. There is an urgent need to develop new therapies
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