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Human induced pluripotent stem cells (hiPSCs) have shown promise in repairing injury in animal BPD models. Evidence suggests they exert their effects via paracrine mechanisms. We aim herein to assess the effectiveness of extracellular vesicles (EVs) derived from hiPSCs and their alveolar progenies (diPSCs) in attenuating hyperoxic injury in a preterm lung explant model.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Murine lung lobes were harvested on embryonic day 17.5 and maintained in air\u2013liquid interface. Following exposure to 95% O<jats:sub>2<\/jats:sub> for 24\u00a0h, media was supplemented with 5\u2009\u00d7\u200910<jats:sup>6<\/jats:sup> particles\/mL of EVs isolated from hiPSCs or diPSCs by size-exclusion chromatography. On day 3, explants were assessed using Hematoxylin\u2013Eosin staining with mean linear intercept (MLI) measurements, immunohistochemistry, <jats:italic>VEGFa<\/jats:italic> and antioxidant gene expression. Statistical analysis was conducted using one-way ANOVA and Multiple Comparison Test. EV proteomic profiling was performed, and annotations focused on alveolarization and angiogenesis signaling pathways, as well as anti-inflammatory, anti-oxidant, and regenerative pathways.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Exposure of fetal lung explants to hyperoxia induced airspace enlargement, increased MLI, upregulation of anti-oxidants <jats:italic>Prdx5<\/jats:italic> and <jats:italic>Nfe2l2<\/jats:italic> with decreased <jats:italic>VEGFa<\/jats:italic> expression. Treatment with hiPSC-EVs improved parenchymal histologic changes. No overt changes in vasculature structure were observed on immunohistochemistry in our in vitro model. However, <jats:italic>VEGFa<\/jats:italic> and anti-oxidant genes were upregulated with diPSC-EVs, suggesting a pro-angiogenic and cytoprotective potential. EV proteomic analysis provided new insights in regard to potential pathways influencing lung regeneration.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This proof-of-concept in vitro study reveals a potential role for hiPSC- and diPSC-EVs in attenuating lung changes associated with prematurity and oxygen exposure. Our findings pave the way for a novel cell free approach to prevent and\/or treat BPD, and ultimately reduce the global burden of the disease.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13287-024-03687-3","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T14:02:32Z","timestamp":1710424952000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effectiveness of extracellular vesicles derived from hiPSCs in repairing hyperoxia-induced injury in a fetal murine lung explant model"],"prefix":"10.1186","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7506-8525","authenticated-orcid":false,"given":"Hala","family":"Saneh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Wanczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Finck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,14]]},"reference":[{"issue":"10","key":"3687_CR1","doi-asserted-by":"publisher","first-page":"e531","DOI":"10.1542\/neo.7-10-e531","volume":"7","author":"AH Jobe","year":"2006","unstructured":"Jobe AH. 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