EXPRESS: The function of microRNAs transported by cell extracellular vesicles in post-stroke recovery: a systematic review

BACKGROUND: Stroke is associated with persistently elevated rates of mortality and disability. Effective cerebroprotection strategies and interventions for promoting functional recovery after stroke remain an unmet need. Cell transplantation represents a potential therapeutic strategy for facilitating brain recovery and regeneration. Its therapeutic benefits are thought to be partly mediated by extracellular vesicles and the various miRNAs they carry, which from different cell sources may exert distinct therapeutic effects. METHODS: We systematically searched PubMed, Embase, and Cochrane Library for original studies on extracellular vesicles in post-stroke recovery, focusing on miRNA mechanisms. Data on cell source, miRNA, in vitro/vivo model, administration, target/pathway, outcomes, and presumed treatment window were extracted. RESULTS: We categorize exosomal miRNAs into three distinct groups based on their cellular origins: mesenchymal stem cells, other stem cells, and non-stem cells. Mesenchymal stem cell-derived extracellular vesicles carry diverse miRNAs regulating angiogenesis, inflammation, apoptosis, autophagy, and neuroplasticity; other stem cell-derived vesicles show source-specific effects; non-stem cell-derived vesicles from astrocytes, microglia, and endothelial cells also modulate neuronal survival and repair. Therapeutic effects span acute cytoprotection, subacute tissue repair, and chronic neuroplasticity. Most miRNAs are supported by at least one in vivo study, while a few rely mainly on in vitro evidence.