Open Access

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

  • Published online on: March 10, 2017     https://doi.org/10.3892/ijmm.2017.2914
  • Pages: 936-948
  • Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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April-2017
Volume 39 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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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