Mesenchymal stem cells ameliorate β cell dysfunction of human type 2 diabetic islets by reversing β cell dedifferentiation.
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.
['Wang|Le|L|', 'Liu|Tengli|T|', 'Liang|Rui|R|', 'Wang|Guanqiao|G|', 'Liu|Yaojuan|Y|', 'Zou|Jiaqi|J|', 'Liu|Na|N|', 'Zhang|Boya|B|', 'Liu|Yan|Y|', 'Ding|Xuejie|X|', 'Cai|Xiangheng|X|', 'Wang|Zhiping|Z|', 'Xu|Xiumin|X|', 'Ricordi|Camillo|C|', 'Wang|Shusen|S|', 'Shen|Zhongyang|Z|']
D000818:Animals D054337:Cell Dedifferentiation D003924:Diabetes Mellitus, Type 2 D005260:Female D006801:Humans D050417:Insulin-Secreting Cells D053590:Interleukin 1 Receptor Antagonist Protein D053583:Interleukin-1beta D008297:Male D045164:Mesenchymal Stem Cell Transplantation D059630:Mesenchymal Stem Cells D016513:Mice, SCID D008875:Middle Aged D014409:Tumor Necrosis Factor-alpha
Mesenchymal stem cells β cell dysfunction β cell dedifferentiation Type 2 diabetes mellitus Inflammation