AUTHOR=Couto Samuel C. F. , Lopes-Pacheco Miquéias , Rocha Vanderson , Dos Santos Claudia C. , Rocco Patricia R. M. 

TITLE=Extracellular vesicles from mesenchymal stromal cells as a promising therapy for ARDS: a systematic review of preclinical studies

JOURNAL=Frontiers in Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1665948

DOI=10.3389/fmed.2025.1665948

ISSN=2296-858X

ABSTRACT=IntroductionMesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising cell-free therapeutic strategy for acute respiratory distress syndrome (ARDS), a condition with limited effective treatment options.MethodsThis systematic review synthesizes findings from 51 in vivo preclinical studies investigating the efficacy, delivery methods, mechanisms of action, and optimization strategies of MSC-EV interventions in experimental ARDS.ResultsAcross diverse models and etiologies, MSC-EVs consistently attenuated inflammation, improved gas exchange, and enhanced survival. Mechanistically, these benefits were largely attributed to microRNA-mediated immunomodulation, including promotion of anti-inflammatory macrophage phenotypes and improved bacterial clearance. Factors influencing therapeutic efficacy included the MSC source, EV preconditioning, timing of administration, and route of delivery.DiscussionDespite these encouraging findings, critical methodological heterogeneity limits reproducibility and translational potential. This heterogeneity is particularly evident in dose metrics (e.g., particle number versus protein content), EV quantification methods (e.g., flow cytometry versus nanoparticle tracking analysis), and timing of outcome assessment. This review underscores the growing body of preclinical evidence supporting MSC-EVs in ARDS and identifies key knowledge gaps such as optimal dosing, safety profiling, and scalable manufacturing that must be addressed to enable clinical translation.