Mesenchymal stem cells ameliorate cell dysfunction of human type 2 diabetic islets by reversing cell dedifferentiation

Background: A physiological hallmark of patients with type 2 diabetes mellitus (T2DM) is beta cell dysfunction. Despite adequate treatment, it is an irreversible process that follows disease progression. Therefore, the development of novel therapies that restore beta 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 beta cell dysfunction by reversing beta 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 beta 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 beta 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 beta cell dysfunction. (C) 2019 The Author(s). Published by Elsevier B.V.