Objective 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. Methods 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. Results 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. Conclusion Stem cell treatment based on MSCs modified to overexpress the FGF21 and GLP1 genes is an effective approach for the treatment of T2DM.

Obesity and its associated metabolic disorders are increasingly impacting public health worldwide. Sphingosine kinase 1 (Sphk1) is a critical enzyme in sphingolipid metabolism that has been implicated in various metabolic syndromes. In this study, we developed a mouse model constitutively expressing pseudoacetylated mouse Sphk1 (QSPHK1) to study its role in regulating glucose and lipid metabolism. The results showed that QSPHK1 mice gained less body weight than wide type (WT) mice on a high-fat diet, and QSPHK1 mice had improved glucolipid metabolism and insulin. Moreover, QSPHK1 mice had alleviated hepatic triglyceride accumulation and had high-fat-diet-induced hepatic steatosis that occurred as a result of reduced lipogenesis and enhanced fatty acid oxidation, which were mediated by the AMPK/ACC axis and the FGF21/adiponectin axis. Collectively, this study provided evidence that the K27Q/K29Q mutations of Sphk1 could have a protective role in preventing obesity and the related metabolic diseases. Hence, our results contribute to further understanding of the biological functions of Sphk1, which has great pharmaceutical implications.

Objective: The purpose of the study was to investigate the therapeutic effects of genetically modified mesenchymal stem cells (MSCs) in the treatment of type 2 diabetes mellitues (T2DM), in order to find a new method of diabetes treatment different from traditional medicine, and provide a new way to fundamentally improve or treat diabetes.Methods: MSCs derived from adipose tissue were modified with over-expression of FGF21 and GLP1, which was achieved through lentiviral particles transduction. The cells were transplanted to the BKS.Cg-Dock7m+/+Leprdb/Nju mice (T2DM mice model). The injections of physiological saline (0.1 mL), Liraglutide (0.5mg/kg) were employed as negative and positive controls respectively. The protein analyses were performed using ELISA or western blot analysis, while quantitative real-time PCR was adopted for gene expression.Results: The genetic modification had no effects on morphology, differentiation ability, or immunophenotype of MSCs. Moreover, MSC-FGF21+GLP1 cells exhibited significantly increased secretion of FGF21 and GLP1. In T2DM model mice, the transplantation of MSC-FGF21+GLP1 cells ameliorated blood glucose and weight, promoted the secretion of insulin, enhanced the recovery of liver structures, and improved lipid profiles. Moreover, FGF21 and GLP1 exhibited synergistic effects in regulation of glucolipid metabolism through controlling the expression of insulin, srebp1 and srebp2.Conclusion: The stem cell treatment based on MSCs modified by FGF21 and GLP1 genes is an effective approach for treatment of T2DM.

Objective: The purpose of the study was to investigate the therapeutic effects and safety of genetic modified mesenchymal stem cells (MSCs) in type 2 diabetes mellitues (T2DM).Methods: MSCs derived from adipose tissue were modified with over-expression of FGF21 and GLP1, which was achieved through lentiviral particles transduction. The cells were transplanted to the BKS.Cg-Dock7m+/+Leprdb/Nju mice (T2DM mice model). The injections of physiological saline (0.1 mL), Liraglutide (0.5mg/kg) were employed as negative and positive controls respectively. The protein analyses were performed using ELISA or western blot analysis, while quantitative real-time PCR was adopted for gene expression.Results: The genetic modification had no effects on morphology, differentiation ability, or immunophenotype of MSCs. Moreover, MSC-FGF21+GLP1 cells exhibited significantly increased expression of FGF21 and GLP1. In T2DM model mice, the transplantation of MSC-FGF21+GLP1 cells ameliorated blood glucose and weight, promoted the secretion of insulin, enhanced the recovery of liver structures, and improved lipid profiles. Moreover, FGF21 and GLP1 exhibited synergistic effects in regulation of glucolipid metabolism through controlling the expression of insulin, srebp1 and srebp2.Conclusion: The stem cell treatment based on MSCs modified by FGF21 and GLP1 genes is an effective approach for treatment of T2DM.

Objective: 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. Methods: 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 were used for protein analysis, and quantitative real-time PCR was used for gene expression analysis. Results: 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. Conclusion: Stem cell treatment based on MSCs modified to overexpress the FGF21 and GLP1 genes is an effective approach for the treatment of T2DM. Key words: Type 2 diabetes mellitus; Mesenchymal stem cell; FGF21; GLP1