Adipose mesenchymal stem cells‐derived exosomes attenuated hyperoxia‐induced lung injury in neonatal rats via inhibiting the NF‐κB signaling pathway

Abstract Objective Bronchopulmonary dysplasia (BPD) is the most common chronic morbidity in extremely preterm infants. Mesenchymal stem cells‐derived exosomes (MSC‐Exos) therapies have shown prospects in animal models of BPD. Our study aimed to evaluate the effect of adipose mesenchymal stem cells‐derived exosomes (AMSC‐Exos) on BPD and the role of the NF‐κB signaling pathway in this process. Methods The AMSCs were extracted and AMSC‐Exos were isolated by ultracentrifugation method. Newborn rats were exposed to hyperoxia (90% O 2 ) continuously for 7 days to establish a BPD model. The rats were treated with AMSC‐Exos by intratracheal administration on postnatal day 4 (P4). Pulmonary morphology, pulmonary vasculature, inflammatory factors, and NF‐κB were assessed. Hyperoxia‐induced primary type II alveolar epithelial cells (AECIIs) and AMSC‐Exos treatment with or without a pan‐NF‐κB inhibitor (PDTC) were established to explore the potential mechanism. Results Hyperoxia‐exposed rats showed alveolar simplification with decreased radial alveolar count and increased mean linear intercept, low CD31, and vascular endothelial growth factor expression, reduced microvessel density, increased the expression of TNF‐α, IL‐1β, and IL‐6 and decreased the expression of IL‐10, and induced NF‐κB phosphorylation. AMSC‐Exos protected the neonatal lung from the hyperoxia‐induced arrest of alveolar and vascular development, alleviated inflammation, and inhibited NF‐κB phosphorylation. Hyperoxia decreased viability, increased apoptosis, enhanced inflammation, and induced NF‐κB phosphorylation of AECIIs but improved by AMSC‐Exos, PDTC, or AMSC‐Exos+PDTC. The effect of AMSC‐Exos+PDTC in AECIIs was the same as AMSC‐Exos, but more notable than PDTC alone. Conclusion AMSC‐Exos attenuated the hyperoxia‐induced lung injury in neonatal rats by inhibiting the NF‐κB signaling pathway partly.