Abstract High‐altitude pulmonary edema (HAPE) is a life‐threatening disorder caused by hypobaric hypoxia and characterized by pulmonary injury, oxidative stress, and inflammation. We investigated the effects of small extracellular vesicles derived from dental pulp stem cells (DPSCs‐sEVs) in a rat model of HAPE as well as hypoxia‐injured pulmonary microvascular endothelial cells (PMVECs). Rats were exposed to hypobaric hypoxia for 96 h. Lung injury was assessed by histology and immunofluorescence (VEGF, TNF‐α, Occludin). Pulmonary permeability was evaluated by total protein in bronchoalveolar lavage fluid and lung homogenates and by Na + /K + ‐ATPase activity. Oxidative stress, inflammatory mediators, and vasoactive factors (NO, PGI₂) were measured. DPSCs‐sEVs attenuated hypoxia‐induced lung injury, increased VEGF and Occludin, reduced TNF‐α, decreased protein leakage, and enhanced Na + /K + ‐ATPase activity. DPSCs‐sEVs alleviated oxidative stress and upregulated Nrf2, HO‐1, and GPX1. In vivo, dexamethasone served as a reference treatment; DPSCs‐sEVs produced greater improvements in most endpoints, with comparable effects in selected measures. In PMVECs, DPSCs‐sEVs dose‐dependently mitigated hypoxia‐induced dysfunction. These findings suggest DPSCs‐sEVs protect against hypoxia‐induced pulmonary injury by preserving barrier integrity and improving redox and inflammatory homeostasis.
Li et al. (Sun,) studied this question.