Immunomodulatory and neuroprotective effects of miR-146a-enriched MSC-derived extracellular vesicles in experimental autoimmune encephalomyelitis.

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)

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as promising cell-free therapeutics due to their immunomodulatory and reparative properties, especially through microRNAs (miRNAs). This study investigates the therapeutic potential of EVs enriched with miR-146a-EVs, a key regulator of inflammatory signaling, in experimental autoimmune encephalomyelitis (EAE), a murine model of MS. Human adipose-derived MSCs (hADSCs) were transfected with miR-146a mimics or miR-control, and their EVs were isolated. After EAE induction in C57BL/6 mice, they were treated intravenously with miR-146a-enriched EVs, control EVs, or PBS. Clinical scores were monitored for 30 days. Cytokine levels (tumor necrosis factor (TNF)-α, interferon-gamma (IFN-γ), interleukin (IL)-17, IL-4, IL-10, transforming growth factor beta (TGF-β)) were measured in splenocytes and spinal cord tissue using enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (qPCR), respectively. Histopathology (Hematoxylin and Eosin (H&E), Luxol Fast Blue (LFB)) and immunohistochemistry (Myelin Basic Protein (MBP)) assessed inflammation and demyelination. miR-146a-enriched EVs significantly attenuated EAE severity, reducing pro-inflammatory cytokines (TNF-α, IFN-γ, IL-17) and elevating anti-inflammatory cytokines (IL-10, TGF-β) in both splenocyte cultures and spinal cord tissue. The

Evidence level

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

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