Microvesicles derived from mesenchymal stem cells inhibit acute respiratory distress syndrome-related pulmonary fibrosis in mouse partly through hepatocyte growth factor

Qi-Hong Chen; Ying Zhang; Xue Gu; Peng-Lei Yang; Jun Yuan; Li-Na Yu; Jian-Mei Chen

doi:10.4252/wjsc.v16.i8.811

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 Aug 26;16(8):811-823. doi: 10.4252/wjsc.v16.i8.811.

Authors

Qi-Hong Chen¹, Ying Zhang², Xue Gu², Peng-Lei Yang², Jun Yuan², Li-Na Yu², Jian-Mei Chen³

Affiliations

¹ Department of Critical Care Medicine, Jiangdu People's Hospital of Yangzhou, Jiangdu People's Hospital Affiliated to Yangzhou University, Yangzhou 225200, Jiangsu Province, China.
² Department of Critical Care Medicine, Jiangdu People's Hospital of Yangzhou, Yangzhou 225200, Jiangsu Province, China.
³ Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225000, Jiangsu Province, China. [email protected].

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.

Keywords: Acute respiratory distress syndrome; Hepatocyte growth factor; Mesenchymal stromal cells; Microvesicles derived from mesenchymal stem cells; Pulmonary fibrosis.