Mesenchymal stem cell-derived small extracellular vesicles alleviate the immunometabolic dysfunction in murine septic encephalopathy.

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)

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection that results in high mortality and long-term sequela. The central nervous system (CNS) is susceptible to injury from infectious processes, which can lead to clinical symptoms of septic encephalopathy (SE). SE is linked to a profound energetic deficit associated with immune dysregulation. Here, we show that intravenous administration of adipose tissue mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) in septic mice improved disease outcomes by reducing SE clinical severity, restoring aerobic metabolism, and lowering pro-inflammatory cytokines in the cerebellum, a key region affected by SE. Our high throughput analysis showed that MSC-derived sEVs partially reversed sepsis-induced transcriptomic changes, highlighting the potential association of miRNA regulators in the cerebellum of MSC-derived sEV-treated mice with miRNAs identified in sEV cargo. MSC-derived sEVs could serve as a promising therapeutic agent in SE through their favorable immunometabolic properties.

Evidence level

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

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