Enhancing insulin sensitivity in type 2 diabetes mellitus using apelin-loaded small extracellular vesicles from Wharton's jelly-derived mesenchymal stem cells: a novel therapeutic approach.

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)

Type 2 diabetes mellitus (T2DM), characterized by β-cell dysfunction and insulin resistance (IR), presents considerable treatment challenges. Apelin is an adipocyte-derived factor that shows promise in improving IR; however, it is limited by poor targeting and a short half-life. In the present study, engineered small extracellular vesicles (sEVs) derived from Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) loaded with apelin were used to address the limitations of the therapeutic application of apelin. WJ-MSCs were transduced to obtain engineered sEVs loaded with overexpressed apelin (apelin-MSC-sEVs) and the control sEVs (MSC-sEVs). T2DM mice were injected with apelin-MSC-sEVs and MSC-sEVs, and blood glucose monitoring, glucose and insulin tolerance tests, confocal microscopy, and immunocytochemical analysis were performed. IR models of 3T3-L1 adipocytes were employed to detect GLUT4 expression in each group using western blotting; the affected pathways were determined by measuring the changes in Akt and AMPK signaling and phosphorylation. Upon successful engineering, WJ-MSCs demonstrated significant overexpression of apelin. The genetic modification did not adversely impact the characteristics of sEVs, ranging from surface protein markers, morphology, to particle size, but generated apelin-overexpressed sEVs. Apelin-MSC-sEVs treatment resulted in notable enhancement

Evidence level

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

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