Mesenchymal stromal cell–derived extracellular vesicles in regenerative medicine: Standardisation, bioengineering and clinical translation

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have emerged as promising cell-free therapeutics that recapitulate key paracrine functions of MSCs whilst mitigating limitations of viable-cell therapies. Clinical translation is hindered by inconsistent dose metrics, lack of validated potency assays, and manufacturing complexities. Here we review advances in MSC-EV standardisation, source and culture determinants, engineering and delivery platforms, and clinical applications, exemplified by chronic wound healing. We operationalise dual-metric dosing (particles <i>plus</i> protein) linked to mechanism-aligned potency assays, adopt a route-aware exposure-response framework to guide delivery strategies, and propose decision matrices aligning MSC sources and bioprocesses with indication-specific tasks. Good Laboratory Practice safety panels and Good Manufacturing Practice scale-up strategies are outlined to support regulatory readiness. Early clinical studies demonstrate feasibility and short-term safety but reveal heterogeneous efficacy, underscoring the need for harmonised dosing and potency measures. Collectively, these insights provide a roadmap to advance MSC-EVs as indication-matched regenerative medicines.