Background:::Mesenchymal stem cell-derived exosomes (MSC-Exos) therapies have
shown prospects in preclinical models of pathologies relevant to neonatal medicine, such as bronchopulmonary
dysplasia (BPD). Adipose-derived stem cells (ADSCs) have been recognized as
one of the most promising stem cell sources. Autophagy plays a key role in regulating intracellular
conditions, maintaining cell growth and development, and participating in the pathogenesis of
BPD.
Objectives:::To investigate the potential therapeutic role of ADSC-Exos on BPD and to illustrate
the role of autophagy in this process.
Method:::ADSC-Exos was isolated from media conditioned of ADSCs by ultracentrifugation and
characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA),
and Western blotting (WB). Newborn rats were exposed to hyperoxia (90% O2) from postnatal
day 0 (P0) to P7, and returned to room air until P14 to mimic BPD. ADSC-Exos was treated by intratracheal
or intravenous administration on P4. Treated animals and appropriate controls were
harvested on P7 and P14 for assessment of pulmonary parameters.
Results:::Hyperoxia-exposed rats were presented with pronounced alveolar simplification with decreased
radial alveolar count (RAC) and increased mean linear intercept (MLI), impaired vascular
development with low vascular endothelial growth factor (VEGF) and CD31 expression, and stimulated
inflammation with increased expression of TNF-α, IL-1β, and IL-6, and decreased expression
of IL-10. Meanwhile, the rats with hyperoxia exposure blocked autophagic flux with lower
levels of Beclin1, LC3B, LC3BII/I ratio and higher levels of p62. ADSC-Exos administration protected
the neonatal lung tissues from the hyperoxia-induced arrest of alveolar and vascular development,
reduced inflammation, and facilitated autophagy. Intratracheal administration was more
efficacious than intravenous administration
Conclusion:::The intratracheal administration of ADSC-Exos significantly improved alveolarization
and pulmonary vascularization arrest in hyperoxia-induced BPD, which was associated with
facilitating autophagy in part.