Mesenchymal stem cells ameliorate β cell dysfunction of human type 2 diabetic islets by reversing β cell dedifferentiation Journal Articles uri icon

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abstract

  • BACKGROUND: A physiological hallmark of patients with type 2 diabetes mellitus (T2DM) is β cell dysfunction. Despite adequate treatment, it is an irreversible process that follows disease progression. Therefore, the development of novel therapies that restore β cell function is of utmost importance. METHODS: This study aims to unveil the mechanistic action of mesenchymal stem cells (MSCs) by investigating its impact on isolated human T2DM islets ex vivo and in vivo. FINDINGS: We propose that MSCs can attenuate β cell dysfunction by reversing β cell dedifferentiation in an IL-1Ra-mediated manner. In response to the elevated expression of proinflammatory cytokines in human T2DM islet cells, we observed that MSCs was activated to secret IL-1R antagonist (IL-1Ra) which acted on the inflammed islets and reversed β cell dedifferentiation, suggesting a crosstalk between MSCs and human T2DM islets. The co-transplantation of MSCs with human T2DM islets in diabetic SCID mice and intravenous infusion of MSCs in db/db mice revealed the reversal of β cell dedifferentiation and improved glycaemic control in the latter. INTERPRETATION: This evidence highlights the potential of MSCs in future cell-based therapies regarding the amelioration of β cell dysfunction.

authors

  • Wang, Le
  • Liu, Tengli
  • Liang, Rui
  • Wang, Guanqiao
  • Liu, Yaojuan
  • Zou, Jiaqi
  • Liu, Na
  • Zhang, Boya
  • Liu, Yan
  • Ding, Xuejie
  • Cai, Xiangheng
  • Wang, Zhiping
  • Xu, Xiumin
  • Ricordi, Camillo
  • Wang, Shusen
  • Shen, Zhongyang

publication date

  • January 2020