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We investigated the effects of small extracellular vesicles derived from dental pulp stem cells (DPSCs\u2010sEVs) in a rat model of HAPE as well as hypoxia\u2010injured pulmonary microvascular endothelial cells (PMVECs). Rats were exposed to hypobaric hypoxia for 96\u2009h. Lung injury was assessed by histology and immunofluorescence (VEGF, TNF\u2010\u03b1, Occludin). Pulmonary permeability was evaluated by total protein in bronchoalveolar lavage fluid and lung homogenates and by Na\n                    <jats:sup>+<\/jats:sup>\n                    \/K\n                    <jats:sup>+<\/jats:sup>\n                    \u2010ATPase activity. Oxidative stress, inflammatory mediators, and vasoactive factors (NO, PGI\u2082) were measured. DPSCs\u2010sEVs attenuated hypoxia\u2010induced lung injury, increased VEGF and Occludin, reduced TNF\u2010\u03b1, decreased protein leakage, and enhanced Na\n                    <jats:sup>+<\/jats:sup>\n                    \/K\n                    <jats:sup>+<\/jats:sup>\n                    \u2010ATPase activity. DPSCs\u2010sEVs alleviated oxidative stress and upregulated Nrf2, HO\u20101, and GPX1. In\u00a0vivo, dexamethasone served as a reference treatment; DPSCs\u2010sEVs produced greater improvements in most endpoints, with comparable effects in selected measures. In PMVECs, DPSCs\u2010sEVs dose\u2010dependently mitigated hypoxia\u2010induced dysfunction. These findings suggest DPSCs\u2010sEVs protect against hypoxia\u2010induced pulmonary injury by preserving barrier integrity and improving redox and inflammatory homeostasis.\n                  <\/jats:p>","DOI":"10.14814\/phy2.70810","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:24:16Z","timestamp":1773005056000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intervention effect of small extracellular vesicles derived from dental pulp stem cells on a high\u2010altitude pulmonary edema model in male rats"],"prefix":"10.14814","volume":"14","author":[{"given":"Xue","family":"Li","sequence":"first","affiliation":[{"name":"Beijing International Science and Technology Cooperation Base for Antiviral Drugs, Beijing Key Laboratory of Environmental and Viral Oncology, College of Chemistry and Life Science Beijing University of Technology  Beijing China"},{"name":"Beijing Institute of Radiation Medicine  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuang","family":"Mao","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changyao","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youwei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiawei","family":"Liu","sequence":"additional","affiliation":[{"name":"National Center of Protein Sciences Beijing  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