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.

中文翻译：

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间充质干细胞通过逆转β细胞去分化来改善人类2型糖尿病胰岛的β细胞功能障碍。

背景技术2型糖尿病（T2DM）患者的生理特征是β细胞功能障碍。尽管有足够的治疗方法，但它是疾病发展后不可逆的过程。因此，开发恢复β细胞功能的新疗法至关重要。方法本研究旨在通过研究离体和离体人间充质干细胞对分离的人T2DM胰岛的影响来揭示其间的机械作用。结果我们提出，MSC可以通过以IL-1Ra介导的方式逆转β细胞去分化来减轻β细胞功能障碍。为了响应人T2DM胰岛细胞中促炎细胞因子的表达升高，我们观察到MSC被激活以分泌IL-1R拮抗剂（IL-1Ra），后者作用于发炎的胰岛并逆转了β细胞去分化，提示MSC与人类T2DM胰岛之间存在串扰。糖尿病人SCID小鼠中MSC与人T2DM胰岛的共移植以及db / db小鼠中MSC的静脉内输注揭示了后者中β细胞去分化的逆转和改善的血糖控制。解释该证据凸显了MSC在改善β细胞功能障碍方面在基于细胞的未来疗法中的潜力。