Mesenchymal stromal cell-derived extracellular vesicles as a next-generation therapy for ARDS: mechanisms, advances, and future directions.

Abstract

Introduction: Acute respiratory distress syndrome (ARDS) is a life-threatening syndrome characterized by diffuse alveolar damage, severe hypoxemia, and dysregulated inflammation. Despite improvements in lung-protective ventilation and supportive care, mortality remains high, highlighting the need for therapies targeting core mechanisms of injury and repair. Mesenchymal stromal cells (MSCs) have demonstrated therapeutic potential largely via paracrine mechanisms, with extracellular vesicles (EVs) emerging as a cell-free alternative that retains key MSC benefits while overcoming limitations related to cell viability, engraftment, and scalability.

Areas covered: This review synthesizes current evidence on MSC-derived EVs (MSC-EVs) in ARDS, encompassing mechanisms of action, preclinical efficacy, delivery strategies, and translational challenges. Studies published from 2015 to 2025 were retrieved from PubMed, Web of Science, and ClinicalTrials.gov. Emphasis is placed on immunomodulatory effects, restoration of alveolar - capillary barrier integrity, and transfer of functional proteins, mRNAs, and microRNAs.

Expert opinion: MSC-EVs represent a promising, disease-modifying therapy with potential to reduce ventilation duration, extracorporeal support, and overall healthcare burden. Key challenges remain, including standardized manufacturing, validated potency assays, and identification of patient selection biomarkers. Integration of bioengineering innovations, GMP-compliant production pipelines, and stratified clinical trial designs will be critical to accelerate translation and enable definitive evaluation in late-phase studies.