Chen QH, Zhang Y, Gu X, Yang PL, Yuan J, Yu LN, Chen JM. Microvesicles derived from mesenchymal stem cells inhibit acute respiratory distress syndrome-related pulmonary fibrosis in mouse partly through hepatocyte growth factor. World J Stem Cells 2024; 16(8): 811-823 [PMID: 39219725 DOI: 10.4252/wjsc.v16.i8.811]
Corresponding Author of This Article
Jian-Mei Chen, PhD, Researcher, Institute of Translational Medicine, Medical College, Yangzhou University, No. 136 Jiangyang Middle Road, Hanjiang District, Yangzhou 225000, Jiangsu Province, China. 18051063567@163.com
Research Domain of This Article
Respiratory System
Article-Type of This Article
Basic Study
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/
Qi-Hong Chen, Department of Critical Care Medicine, Jiangdu People’s Hospital of Yangzhou, Jiangdu People’s Hospital Affiliated to Yangzhou University, Yangzhou 225200, Jiangsu Province, China
Ying Zhang, Xue Gu, Peng-Lei Yang, Jun Yuan, Li-Na Yu, Department of Critical Care Medicine, Jiangdu People’s Hospital of Yangzhou, Yangzhou 225200, Jiangsu Province, China
Jian-Mei Chen, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225000, Jiangsu Province, China
Author contributions: Chen QH designed the study and wrote the manuscript; Zhang Y participated in the cell culture and molecular biology experiments; Gu X performed the animal experiments and data acquisition; Yang PL contributed to the data acquisition and statistical analysis; Yuan J helped with the animal experiments and data acquisition; Yu LN performed the molecular biology experiments and statistical analyses; Chen JM contributed to research quality control and manuscript revision; All authors approved the final manuscript.
Supported byResearch Project of Jiangsu Provincial Health Commission, No. Z2022008; and Research Project of Yangzhou Health Commission, No. 2023-2-27.
Institutional animal care and use committee statement: Animal care and interventions were performed in accordance with the National Institute of Health Guide for the Care and Use of Experimental Animals, and the animal protocol (YXYLL-2022-103) was approved by the Institutional Animal Care and Use Committees of the Yangzhou University School of Medicine.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available upon reasonable request from the corresponding author at 18051063567@163.com.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Jian-Mei Chen, PhD, Researcher, Institute of Translational Medicine, Medical College, Yangzhou University, No. 136 Jiangyang Middle Road, Hanjiang District, Yangzhou 225000, Jiangsu Province, China. 18051063567@163.com
Received: March 19, 2024 Revised: July 4, 2024 Accepted: August 15, 2024 Published online: August 26, 2024 Processing time: 159 Days and 23 Hours
Abstract
BACKGROUND
Pulmonary fibrosis is one of the main reasons for the high mortality rate among acute respiratory distress syndrome (ARDS) patients. Mesenchymal stromal cell-derived microvesicles (MSC-MVs) have been shown to exert antifibrotic effects in lung diseases.
AIM
To investigate the effects and mechanisms of MSC-MVs on pulmonary fibrosis in ARDS mouse models.
METHODS
MSC-MVs with low hepatocyte growth factor (HGF) expression (siHGF-MSC-MVs) were obtained via lentivirus transfection and used to establish the ARDS pulmonary fibrosis mouse model. Following intubation, respiratory mechanics-related indicators were measured via an experimental small animal lung function tester. Homing of MSC-MVs in lung tissues was investigated by near-infrared live imaging. Immunohistochemical, western blotting, ELISA and other methods were used to detect expression of pulmonary fibrosis-related proteins and to compare effects on pulmonary fibrosis and fibrosis-related indicators.
RESULTS
The MSC-MVs gradually migrated and homed to damaged lung tissues in the ARDS model mice. Treatment with MSC-MVs significantly reduced lung injury and pulmonary fibrosis scores. However, low expression of HGF (siHGF-MSC-MVs) significantly inhibited the effects of MSC-MVs (P < 0.05). Compared with the ARDS pulmonary fibrosis group, the MSC-MVs group exhibited suppressed expression of type I collagen antigen, type III collagen antigen, and the proteins transforming growth factor-β and α-smooth muscle actin, whereas the siHGF-MVs group exhibited significantly increased expression of these proteins. In addition, pulmonary compliance and the pressure of oxygen/oxygen inhalation ratio were significantly lower in the MSC-MVs group, and the effects of the MSC-MVs were significantly inhibited by low HGF expression (all P < 0.05).
CONCLUSION
MSC-MVs improved lung ventilation functions and inhibited pulmonary fibrosis in ARDS mice partly via HGF mRNA transfer.
Core Tip: Pulmonary fibrosis is strongly associated with poor outcomes in acute respiratory distress syndrome (ARDS) patients. Currently, there are no effective measures for treating pulmonary fibrosis. Microvesicles derived from mesenchymal stromal cells (MSC-MVs) have anti-pulmonary fibrosis effects; however, their specific effects and mechanisms in ARDS-related pulmonary fibrosis have not been fully established. This study revealed that MSC-MVs inhibited ARDS-related pulmonary fibrosis and fibrosis-related factors partly through hepatocyte growth factor, improved lung compliance and ventilation functions, and increased oxygenation indices. This study provides a new direction for the treatment of ARDS-related pulmonary fibrosis.
