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

BACKGROUND

Newswise — 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.

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

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.

• Citation: 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
• URL: https://www.wjgnet.com/1948-0210/full/v16/i8/811.htm
• DOI: https://dx.doi.org/10.4252/wjsc.v16.i8.811