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Differentiation of Human Pluripotent Stem Cells Into Pancreatic Beta-Cell Precursors in a 2D Culture System
Published on: December 16, 2021
Mesenchymal stem cells ameliorate β cell dysfunction of human type 2 diabetic islets by reversing β cell
Le Wang1, Tengli Liu2, Rui Liang2
1Organ Transplant Centre, Tianjin First Central Hospital, Nankai University, Tianjin 300192, China; NHC Key Laboratory for Critical Care Medicine, Tianjin 300384, China.
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.
Insights
Mesenchymal stem cells (MSCs) can restore pancreatic beta cell function in type 2 diabetes by reversing dedifferentiation. This IL-1Ra-mediated mechanism improves glycemic control, offering potential for new cell-based therapies.
Area of Science:
- Endocrinology
- Stem Cell Biology
- Diabetes Research
Background:
- Type 2 diabetes mellitus (T2DM) is characterized by progressive beta cell dysfunction.
- Current treatments do not fully restore beta cell function.
- Novel therapeutic strategies are crucial for T2DM management.
Purpose of the Study:
- To investigate the therapeutic potential of mesenchymal stem cells (MSCs) in T2DM.
- To elucidate the mechanism by which MSCs impact beta cell function.
- To evaluate MSCs' effect on isolated human T2DM islets ex vivo and in vivo.
Main Methods:
- Investigated MSCs' impact on isolated human T2DM islets.
- Assessed MSCs' effect in ex vivo and in vivo models.
- Utilized co-transplantation in diabetic SCID mice and intravenous infusion in db/db mice.
Main Results:
- MSCs secrete IL-1R antagonist (IL-1Ra) in response to inflammatory cytokines.
- IL-1Ra from MSCs reversed beta cell dedifferentiation in inflamed human T2DM islets.
- MSC co-transplantation and infusion improved glycemic control and reversed beta cell dedifferentiation in vivo.
Conclusions:
- MSCs show potential for ameliorating beta cell dysfunction in T2DM.
- The IL-1Ra-mediated reversal of beta cell dedifferentiation is a key mechanism.
- MSC-based therapies offer a promising avenue for T2DM treatment.
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