Dual role and clinical application of extracellular vesicles in acute respiratory distress syndrome: Mechanism analysis and translational challenges

Acute respiratory distress syndrome (ARDS) is a severe and life-threatening manifestation of acute lung injury, characterized by widespread pulmonary inflammation and edema, ultimately resulting in acute respiratory failure. Despite advancements in mechanical ventilation and lung-protective strategies, targeted therapies aimed at modulating dysregulated inflammation and promoting tissue repair remain elusive. Extracellular vesicles (EVs), critical mediators of intercellular communication, have emerged as a promising research focus due to their dual regulatory roles in ARDS pathogenesis. Pro-inflammatory EVs, derived from pathogens or injury-stressed cells, exacerbate alveolar macrophage activation and increase endothelial permeability, thereby aggravating pulmonary damage. In contrast, anti-inflammatory EVs originating from mesenchymal stem cells facilitate alveolar barrier restoration and tissue repair by delivering reparative molecular cargo. This review systematically evaluates the dualistic functions of EVs in ARDS from three key perspectives: Molecular mechanisms, clinical translation, and technical challenges. We further discuss the complexities associated with EV heterogeneity, pathogen interactions, and standardization in EV production. Additionally, we propose future directions that integrate engineered EV modifications and multi-omics approaches to address current therapeutic limitations and enhance ARDS management.