Safwan M, Bourgleh MS, Al-Ruqi A, Shrebaty O, Almujaydil F, AlOthaim B, AlRashidi N, Haider KH. Living bio-drug therapies using mesenchymal stem cells and exosomes for mechanically ventilated patients with acute respiratory distress syndrome: A systematic review and meta-analysis. World J Stem Cells 2025; 17(10): 111978 [DOI: 10.4252/wjsc.v17.i10.111978]
Corresponding Author of This Article
Khawaja Husnain Haider, PhD, Professor, Department of Basic Sciences, Sulaiman Al Rajhi University, PO Box 777, Al Bukairiyah 51941, AlQaseem, Saudi Arabia. khhaider@gmail.com
Research Domain of This Article
Cell & Tissue Engineering
Article-Type of This Article
Meta-Analysis
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/
Oct 26, 2025 (publication date) through Oct 27, 2025
Times Cited of This Article
Times Cited (0)
Journal Information of This Article
Publication Name
World Journal of Stem Cells
ISSN
1948-0210
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Share the Article
Safwan M, Bourgleh MS, Al-Ruqi A, Shrebaty O, Almujaydil F, AlOthaim B, AlRashidi N, Haider KH. Living bio-drug therapies using mesenchymal stem cells and exosomes for mechanically ventilated patients with acute respiratory distress syndrome: A systematic review and meta-analysis. World J Stem Cells 2025; 17(10): 111978 [DOI: 10.4252/wjsc.v17.i10.111978]
World J Stem Cells. Oct 26, 2025; 17(10): 111978 Published online Oct 26, 2025. doi: 10.4252/wjsc.v17.i10.111978
Living bio-drug therapies using mesenchymal stem cells and exosomes for mechanically ventilated patients with acute respiratory distress syndrome: A systematic review and meta-analysis
Moaz Safwan, Mariam Safwan Bourgleh, Abdulsalam Al-Ruqi, Omran Shrebaty, Faisal Almujaydil, Basel AlOthaim, Nasser AlRashidi, Khawaja Husnain Haider, Department of Basic Sciences, Sulaiman Al Rajhi University, Al Bukairiyah 51941, AlQaseem, Saudi Arabia
Co-first authors: Moaz Safwan and Mariam Safwan Bourgleh.
Author contributions: Safwan M, Bourgleh MS, and Haider KH participated in manuscript writing; Haider KH designed the study protocol, revised the manuscript, and submitted the paper to the journal; Safwan M registered the study protocol on PROSPERO and performed data extraction; Bourgleh MS performed the statistical analysis; Al-Ruqi A and Shrebaty O performed database screening and reports inclusion; Almujaydil F, AlOthaim B, and AlRashidi N conducted data extraction and quality assessment of the included reports. Safwan M and Bourgleh MS contributed equally to this manuscript and are co-first authors.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: Khawaja Husnain Haider, PhD, Professor, Department of Basic Sciences, Sulaiman Al Rajhi University, PO Box 777, Al Bukairiyah 51941, AlQaseem, Saudi Arabia. khhaider@gmail.com
Received: July 15, 2025 Revised: August 28, 2025 Accepted: October 13, 2025 Published online: October 26, 2025 Processing time: 102 Days and 9.3 Hours
Abstract
BACKGROUND
Mesenchymal stem cells (MSCs), as a living bio-drug, are being considered as a potential treatment for coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome (ARDS) due to their immunomodulatory and reparative properties.
AIM
To synthesize the existing evidence on MSCs and their derivative exosomes for treating COVID-19-induced ARDS, with a focus on the key outcomes of safety and efficacy.
METHODS
Four databases were systematically searched for randomized controlled trials assessing MSCs and their derived exosomes for COVID-19-induced ARDS treatment. Their safety and efficacy were evaluated based on the duration of mechanical ventilation, hospital and intensive care unit stay, 6-minute walk distance, mortality rates, and adverse events. Weighted mean differences and odds ratios with 95% confidence intervals (CIs) were calculated to estimate treatment outcomes: A network meta-analysis (NMA) evaluated mortality, adverse events, and the number of ventilation-free days.
RESULTS
Sixteen randomized controlled trials involving 1027 ARDS patients were included, with 574 receiving MSCs or MSC-derived exosomes. MSC-based therapy did not significantly improve mechanical ventilation duration, ventilation-free days, hospital or intensive care unit stay, or 6-minute walk distance. Sensitivity analysis revealed a significant reduction in mechanical ventilation duration when excluding an outlier (weighted mean difference: -4.84 days; 95%CI: -8.21 to -1.47; I2 = 20%). In contrast, no significant differences were observed in the other outcomes. Mortality and adverse events were comparable between the groups (odds ratio for mortality: 0.77; 95%CI: 0.56-1.06). An NMA of ventilation-free days, mortality, and adverse events revealed no significant difference among MSCs, exosomes, and controls. Exosomes ranked highest in terms of probability of benefit, although without statistical significance.
CONCLUSION
MSC and exosome-based therapies were found to be safe and associated with a reduced duration of mechanical ventilation in patients with ARDS. NMA showed that exosome-based therapy matched the benefits of its parent cells, but with practical and logistical advantages.
Core Tip: Mesenchymal stem cells, as a living bio-drug, are being considered as a potential treatment for coronavirus disease 2019-induced acute respiratory distress syndrome due to their immunomodulatory and reparative properties. Our systematic review and meta-analysis, involving 16 randomized controlled trials (n = 1027 acute respiratory distress syndrome patients), is the first study to directly compare the therapeutic benefits of mesenchymal stem cell-based and their derivative exosome-based therapeutic approaches. Although we did not find significant differences in their safety profiles and efficacy, the exosome-based treatment ranked higher in terms of therapeutic benefits in a network meta-analysis, offering practical and logistical advantages.
