Dermal Fibroblasts-derived Exosomes Alleviated Bronchopulmonary Dysplasia in Neonatal Rats Partially by Regulating Autophagy.

Objective: Bronchopulmonary dysplasia (BPD), a prevalent chronic pulmonary disorder predominantly affecting preterm infants, is characterized by impaired lung development and persistent inflammatory-mediated lung injury. Dermal fibroblast-derived exosomes (DF-Exos) have been demonstrated to alleviate inflammation and promote epithelial tissue repair; however, their role in lung injury remains to be elucidated. This study aimed to evaluate the effects of DF-Exos on BPD and explore their relationship with autophagy.

Methods: DF-Exos were isolated using the ultracentrifugation method. Neonatal Sprague-Dawley (SD) rats were exposed to hyperoxic conditions (90% O₂) for 7 days to establish a BPD model. Lung morphology, pulmonary vasculature, and the expression of inflammatory mediators were assessed. The expressions of autophagy-related proteins Beclin1, LC3B, and p62 were detected to evaluate autophagy.

Results: Neonatal rats exposed to hyperoxic conditions showed alveolar simplification, reduced microvascular density, and a significant upregulation of pro-inflammatory mediators, including IL-1β, IL-6, and TNF-α. In contrast, the levels of the anti-inflammatory cytokine IL-10 showed no statistically significant alteration. The expression of autophagy-related protein Beclin1 and LC3B conversion decreased, and p62 accumulated. DF-Exos administration improved alveolar development, increased microvascular density, alleviated inflammation, facilitated the expression of Beclin1 and the conversion of LC3B, and reduced the expression of p62.

Discussion: Our study showed that in the BPD model, DF-Exos can promote alveolar repair and vascular regeneration, modulate inflammatory responses, and enhance autophagic activity. However, they may also cause transient lung injury in the early stages of development. This effect may be influenced by mild immune rejection. Further studies are needed to elucidate the underlying mechanisms and determine a safe therapeutic dose.

Conclusion: DF-Exos partly ameliorated lung injury in the hyperoxia-induced BPD model, prospectively by enhancing autophagy.