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

## TL;DR

This review summarizes preclinical studies showing that extracellular vesicles from mesenchymal stromal cells may help treat ARDS by reducing inflammation and improving survival.

## Contribution

The paper systematically reviews preclinical evidence and highlights methodological inconsistencies hindering translation of MSC-EVs for ARDS.

## Key findings

- MSC-EVs consistently reduced inflammation and improved survival in ARDS models.
- Therapeutic effects were linked to microRNA-mediated immunomodulation and bacterial clearance.
- Variability in dosing and measurement methods limits reproducibility and clinical translation.

## Abstract

Mesenchymal 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.

This 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.

Across 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.

Despite 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.