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Transplantation of betatrophin-expressing adipose-derived mesenchymal stem cells induces β-cell proliferation in diabetic mice

  • Authors:
    • Liang-Liang Sun
    • Tian-Jin Liu
    • Limei Li
    • Wei Tang
    • Jun-Jie Zou
    • Xiang-Fang Chen
    • Jiao-Yang Zheng
    • Bei-Ge Jiang
    • Yong-Quan Shi
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, P.R. China, Institute of Biochemistry and Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, P.R. China, Clinical and Translational Research Center Shanghai East Hospital, Key Laboratory of Arrhythmias of Ministry of Education, Shanghai 200120, P.R. China, Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, P.R. China
    Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 936-948
    |
    Published online on: March 10, 2017
       https://doi.org/10.3892/ijmm.2017.2914
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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.
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Sun L, Liu T, Li L, Tang W, Zou J, Chen X, Zheng J, Jiang B and Shi Y: Transplantation of betatrophin-expressing adipose-derived mesenchymal stem cells induces β-cell proliferation in diabetic mice. Int J Mol Med 39: 936-948, 2017.
APA
Sun, L., Liu, T., Li, L., Tang, W., Zou, J., Chen, X. ... Shi, Y. (2017). Transplantation of betatrophin-expressing adipose-derived mesenchymal stem cells induces β-cell proliferation in diabetic mice. International Journal of Molecular Medicine, 39, 936-948. https://doi.org/10.3892/ijmm.2017.2914
MLA
Sun, L., Liu, T., Li, L., Tang, W., Zou, J., Chen, X., Zheng, J., Jiang, B., Shi, Y."Transplantation of betatrophin-expressing adipose-derived mesenchymal stem cells induces β-cell proliferation in diabetic mice". International Journal of Molecular Medicine 39.4 (2017): 936-948.
Chicago
Sun, L., Liu, T., Li, L., Tang, W., Zou, J., Chen, X., Zheng, J., Jiang, B., Shi, Y."Transplantation of betatrophin-expressing adipose-derived mesenchymal stem cells induces β-cell proliferation in diabetic mice". International Journal of Molecular Medicine 39, no. 4 (2017): 936-948. https://doi.org/10.3892/ijmm.2017.2914
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Spandidos Publications style
Sun L, Liu T, Li L, Tang W, Zou J, Chen X, Zheng J, Jiang B and Shi Y: Transplantation of betatrophin-expressing adipose-derived mesenchymal stem cells induces β-cell proliferation in diabetic mice. Int J Mol Med 39: 936-948, 2017.
APA
Sun, L., Liu, T., Li, L., Tang, W., Zou, J., Chen, X. ... Shi, Y. (2017). Transplantation of betatrophin-expressing adipose-derived mesenchymal stem cells induces β-cell proliferation in diabetic mice. International Journal of Molecular Medicine, 39, 936-948. https://doi.org/10.3892/ijmm.2017.2914
MLA
Sun, L., Liu, T., Li, L., Tang, W., Zou, J., Chen, X., Zheng, J., Jiang, B., Shi, Y."Transplantation of betatrophin-expressing adipose-derived mesenchymal stem cells induces β-cell proliferation in diabetic mice". International Journal of Molecular Medicine 39.4 (2017): 936-948.
Chicago
Sun, L., Liu, T., Li, L., Tang, W., Zou, J., Chen, X., Zheng, J., Jiang, B., Shi, Y."Transplantation of betatrophin-expressing adipose-derived mesenchymal stem cells induces β-cell proliferation in diabetic mice". International Journal of Molecular Medicine 39, no. 4 (2017): 936-948. https://doi.org/10.3892/ijmm.2017.2914
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