Binghua Xue1, Xiuxiao Xiao2, Tingting Yu2, Xinhua Xiao3, Jing Xie2, Qiuhe Ji4, Li Wang4, Tao Na5, Shufang Meng5, Lingjia Qian6, Haifeng Duan7. 1. Department of Military Cognitive and Stress Medicine, Institute of Military Cognitive and Brain Sciences, Academy of Military Sciences, Beijing, 100850, China. 2. Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Academy of Military Sciences, Beijing, 100850, China. 3. Department of Endocrinology, Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital, Beijing, 100730, China. 4. Department of Endocrinology and Metabolism, Xijing Hospital of Airforce Medical University, Xi'an, 710032, Shanxi, China. 5. The Cell Collection and Research Center, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing, 100050, China. 6. Department of Military Cognitive and Stress Medicine, Institute of Military Cognitive and Brain Sciences, Academy of Military Sciences, Beijing, 100850, China. newjia@vip.sina.com. 7. Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Academy of Military Sciences, Beijing, 100850, China. haifengduan731126@126.com.
Abstract
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.
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.
Entities:
Keywords:
FGF21; GLP1; Mesenchymal stem cell; Type 2 diabetes mellitus
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