Extracellular vesicles MicroRNAs in stroke therapy: recent advances and translational potential

Ischemic stroke accounts for ∼ 87% of all strokes. Existing reperfusion therapies are limited by narrow time windows. Small extracellular vesicles (sEVs) can cross the blood-brain barrier and deliver microRNAs (miRNAs) that modulate post-stroke inflammation, apoptosis, angiogenesis, and neurogenesis. However, most evidence is from preclinical studies (MCAO models), and no approved clinical protocols exist. This review summarizes ischemic stroke pathogenesis and critically evaluates preclinical advances in sEV-miRNA therapy. We highlight key translational barriers: lack of standardized sEV isolation (MISEV2023), miRNA cargo heterogeneity, dosing uncertainties, limited biodistribution data, off-target risks, regulatory bottlenecks, and absence of stroke-specific trials. We also evaluate exosomal miRNAs from various cell sources (e.g., bone marrow mesenchymal stem cells). This review provides a critical synthesis of preclinical evidence to establish a foundation for future translational research in precision stroke therapy.