title: Transplantation of betatrophin-expressing adipose-derived mesenchymal stem cells induces β-cell proliferation in diabetic mice.
abstract: Recent progress in regenerative medicine has suggested that mesenchymal stem cell (MSC)-based therapy is a novel potential cure for diabetes. Betatrophin is a newly identified hormone that can increase the production and expansion of insulin-secreting β-cells when administered to mice. In this study, we evaluated the effect of betatrophin overexpression by human adipose-derived MSCs (ADMSCs) by in vitro experiments, as well as following their transplantation into a mice with streptozotocin (STZ)-induced diabetes. The overexpression of betatrophin did not affect the ADMSCs in terms of proliferation, differentiation and morphology. However, the co-culture of human islets with ADMSCs overexpressing betatrophin (ADMSCs-BET) induced islet proliferation, β-cell specific transcription factor expression, and the islet production of insulin under the stimulation of glucose or KCl and Arg. In addition, ADMSCs-BET enhanced the anti-inflammatory and anti-apoptotic effects of the co-cultured islets compared with ADMSCs cultured alone. In mice with STZ-induced diabetes, the transplantation of ADMSCs-BET ameliorated the hyperglycemia and weight loss associated with STZ-induced diabetes; ADMSCs-BET also significantly enhanced the ratio of β-cells per islet compared to the transplantation of ADMSCs alone. Thus, our study demonstrates a novel strategy for inducing β-cell regeneration. ADMSCs-BET may replace insulin injections by increasing the number of endogenous insulin-producing cells in patients with diabetes. This combined strategy of ADMSC transplantation and gene therapy may prove to be a useful therapy for the treatment of diabetes.
authors.affiliation: Department of Endocrinology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Liang-Liang
authors.initials: LL
authors.lastname: Sun
authors.affiliation: Institute of Biochemistry and Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China.
authors.forename: Tian-Jin
authors.initials: TJ
authors.lastname: Liu
authors.affiliation: Clinical and Translational Research Center Shanghai East Hospital, Key Laboratory of Arrhythmias of Ministry of Education, Shanghai 200120, P.R. China.
authors.forename: Limei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Endocrinology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Zou
authors.affiliation: Department of Endocrinology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Xiang-Fang
authors.initials: XF
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Jiao-Yang
authors.initials: JY
authors.lastname: Zheng
authors.affiliation: Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, P.R. China.
authors.forename: Bei-Ge
authors.initials: BG
authors.lastname: Jiang
authors.affiliation: Department of Endocrinology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, P.R. China.
authors.forename: Yong-Quan
authors.initials: YQ
authors.lastname: Shi
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D064593:Heterografts; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D036361:Peptide Hormones / Q000096:biosynthesis*
chemical_list: C576683:ANGPTL8 protein, human; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D036361:Peptide Hormones