Extracellular Vesicles Derived From Mesenchymal Stem Cells Ameliorate Bronchopulmonary Dysplasia in Mle-12 Cells and Neonatal Mice by Downregulating Mir-34A.

BACKGROUND

Bronchopulmonary dysplasia (BPD) represents a multifaceted, chronic lung disorder caused by extensive oxygen exposure. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been increasingly reported to impact cellular survival, apoptosis, and immune responses. This investigation aimed to delineate the roles and underlying mechanisms of MSC-EVs in hyperoxia-induced MLE-12 cells and BPD mouse model.

METHODS

MSC-EVs were characterized using scanning electron microscopy, nanoparticle tracking analysis, and Western blot assays. After a postnatal animal model of experimental murine BPD was induced by hyperoxia, the morphology of lung tissues was assessed by hematoxylin-eosin and Masson trichrome staining. Gene expression levels were detected using reverse transcription quantitative polymerase chain reaction and Western blot assays. The Cell Counting Kit 8 assay was used to detect cell viability, and the concentrations of caspase 3, caspase 6, collagen type I, and collagen type IV were evaluated through enzyme-linked immunosorbent assay. Gene expression in pulmonary tissues and cells was detected through immunofluorescence, immunohistochemistry, and fluorescence in situ hybridization techniques.

RESULTS

Exposure to MSC-EVs promoted the viability, reduced the apoptosis, altered the alveolar type II cell surface marker surfactant protein C expression, and decreased collagen levels in hyperoxia-induced MLE-12 cells in vitro. In vivo, MSC-EVs mitigated pulmonary damage in hyperoxia-treated mice. Intriguingly, our analyses revealed that MSC-EVs modulated the expression of miR-34a and its downstream gene, macrophage scavenger receptor 1 (MSR1), in murine lung tissues. MSC-EVs or inhibition of miR-34a might aggravate the effects of MSR1 overexpression on lung morphology in vivo.

CONCLUSION

In summary, this research highlights the potential of MSC-EVs in improving pulmonary damage and function via the miR-34a/MSR1 signaling pathway. Thus, MSC-EVs-based therapy may possess great potential in BPD management.