Adipose-derived mesenchymal stem cell-derived extracellular vesicles reduce glycolysis and polarize macrophages toward M2 phenotype in sepsis-associated acute kidney injury via the miR-574-5p/GLUT1 axis.

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)

Extracellular vesicles (EVs) from adipose-derived mesenchymal stem cells (ADSCs) may exert a therapeutic benefit in sepsis-associated organ dysfunction by delivering cargos to target cells. The aims of this study were to explore the therapeutic efficacy and potential mechanism of microRNA (miR)-574-5p delivered by ADSC-EVs in sepsis-associated acute kidney injury (SA-AKI). EVs were isolated from mouse ADSCs and characterized by multilineage differentiation potency, morphology, and surface markers. miR-574-5p expression in ADSC-EVs was analyzed by biochemical testing. Luciferase reporter and RNA pull-down assays were employed to identify the binding relation between miR-574-5p and glucose transporter 1 (GLUT1). Cecal ligation and puncture (CLP)-induced mouse SA-AKI model administered with ADSC-EVs was used to evaluate therapeutic effects on kidney injury. ADSC-EVs were co-cultured with RAW264.7 macrophages to assess effects on inflammation, glycolysis (lactate levels, extracellular acidification rate), and macrophage polarization. ADSC-EVs elevated miR-574-5p expression and polarized macrophages toward M2 phenotype, reducing kidney dysfunction and inflammatory response in CLP mice. In vitro, ADSC-EVs arrested lipopolysaccharide-induced M1 macrophage polarization and induced M2 macrophage polarization by upregulating miR-574-5p expression. Mechanistically, ADSC-EVs transferred mi

Evidence level

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

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