Human umbilical cord-derived mesenchymal stem cells direct macrophage polarization to alleviate pancreatic islets dysfunction in type 2 diabetic mice

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Progressive pancreatic β-cell dysfunction is recognized as a fundamental pathology of type 2 diabetes (T2D). Recently, mesenchymal stem cells (MSCs) have been identified in protection of islets function in T2D individuals. However, the underlying mechanisms remain elusive. It is widely accepted that β-cell dysfunction is closely related to improper accumulation of macrophages in the islets, and a series of reports suggest that MSCs possess great immunomodulatory properties by which they could elicit macrophages into an anti-inflammatory M2 state. In this study, we induced a T2D mouse model with a combination of high-fat diet (HFD) and low-dose streptozotocin (STZ), and then performed human umbilical cord-derived MSCs (hUC-MSCs) infusion to investigate whether the effect of MSCs on islets protection was related to regulation on macrophages in pancreatic islets. hUC-MSCs infusion exerted anti-diabetic effects and significantly promoted islets recovery in T2D mice. Interestingly, pancreatic inflammation was remarkably suppressed, and local M1 macrophages were directed toward an anti-inflammatory M2-like state after hUC-MSC infusion. In vitro study also proved that hUC-MSCs inhibited the activation of the M1 phenotype and induced the generation of the M2 phenotype in isolated mouse bone marrow-derived macrophages (BMDMs), peritoneal macrophages (PMs) and in THP-1 cells. Further ana

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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