Tie YF, Liu H, Zhang T, Meng TW, Liang Q. Dual role and clinical application of extracellular vesicles in acute respiratory distress syndrome: Mechanism analysis and translational challenges. World J Stem Cells 2025; 17(9): 108657 [DOI: 10.4252/wjsc.v17.i9.108657]
Corresponding Author of This Article
Qun Liang, MD, PhD, Chief Physician, Full Professor, Professor, Department of Critical Care Medicine, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, No. 24 Heping Road, Xiangfang District, Harbin 150000, Heilongjiang Province, China. liangqun1@sina.com
Research Domain of This Article
Cell Biology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. Sep 26, 2025; 17(9): 108657 Published online Sep 26, 2025. doi: 10.4252/wjsc.v17.i9.108657
Dual role and clinical application of extracellular vesicles in acute respiratory distress syndrome: Mechanism analysis and translational challenges
Yi-Fu Tie, Han Liu, Tong Zhang, Tian-Wei Meng, Qun Liang
Yi-Fu Tie, Tong Zhang, Tian-Wei Meng, Heilongjiang University of Chinese Medicine, Harbin 150000, Heilongjiang Province, China
Yi-Fu Tie, Ordos Hospital of Traditional Chinese Medicine, Ordos 017000, Inner Mongolia Autonomous Region, China
Han Liu, Institute for Global Health, University College London, London WC1H 0AW, United Kingdom
Qun Liang, Department of Critical Care Medicine, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin 150000, Heilongjiang Province, China
Author contributions: Tie YF, Liu H, Zhang T, Meng TW, and Liang Q contributed substantially to data interpretation and critically reviewed the manuscript; Tie YF wrote the manuscript; Liu H, Zhang T, and Meng TW revised the manuscript and validated its key intellectual elements; Liang Q provided critical oversight of the study design. All authors have read and approved the final version.
Supported by National Natural Science Foundation of China, No. 82374400; and Heilongjiang Province “Double First-Class” New Round of Construction Disciplines Collaborative Innovation Achievements Construction Project, No. LJGXCG2022-097.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Qun Liang, MD, PhD, Chief Physician, Full Professor, Professor, Department of Critical Care Medicine, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, No. 24 Heping Road, Xiangfang District, Harbin 150000, Heilongjiang Province, China. liangqun1@sina.com
Received: April 21, 2025 Revised: May 14, 2025 Accepted: August 21, 2025 Published online: September 26, 2025 Processing time: 157 Days and 17.2 Hours
Abstract
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.
Core Tip: Acute respiratory distress syndrome, a critical illness with a mortality of over 35%, is driven by dysregulated pulmonary inflammation and alveolar injury. Extracellular vesicles (EVs) demonstrate dual regulatory functions - pathogen-derived pro-inflammatory EVs exacerbate macrophage-driven injury, while mesenchymal stem cell EVs suppress inflammation and enhance tissue repair. Current research focuses on EV heterogeneity, spatiotemporal functional dynamics, and clinical translation barriers in therapeutic development. This synthesis integrates mechanistic insights, biomarker advancements, and engineered EV strategies, emphasizing standardization challenges and biosafety considerations. Emerging interdisciplinary approaches, combining multi-omics profiling, nanotechnology, and machine learning, aim to refine EV-based diagnostics and therapeutics, offering transformative potential for acute respiratory distress syndrome management.
