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BPD results in serious respiratory and neurological dysfunctions and mortality. Recently, some clinical trials have commenced using intravenous delivery of donor-derived multilineage-differentiating stress enduring (Muse) cells. In the present study, we aimed to investigate the therapeutic effects of human Muse cells in hyperoxia-induced neonatal lung injury in a rat model with features of bronchopulmonary dysplasia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Rats were put into the incubator within 24\u00a0h from birth to expose to hyperoxia (83%) until postnatal day 15. Muse and non-Muse cells, obtained from the bone marrow-mesenchymal stromal cells (MSCs) as stage-specific embryonic antigen-3 (SSEA-3)+\u2009and \u2212, respectively, were administered slowly via the right external jugular vein or trachea (Muse cells only) on postnatal day 5. For the vehicle groups, only the acetic acid Ringer's solution was administered.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Respiratory function, histological findings, and inflammatory parameters did not differ significantly between intravenous and intratracheal administration. In contrast, body weight gain and survival were worse following intratracheal administration. Intravenous administration of Muse cells resulted in superior amelioration of lung tissue injury, inflammation, and pulmonary hypertension compared with non-Muse cells. We also confirmed the engraftment of Muse cells in the lung tissues. Proteomic profiling identified hyperoxia-induced lung injury associated changes in the abundance of proteins annotated to cell adhesion and coagulation\/fibrinolysis-related pathways, and Muse cell administration was associated with differential abundance of subsets of these proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings suggest that intravenously transplanted Muse cells provide functional benefits in hyperoxia-induced lung injury in a rat model with features of bronchopulmonary dysplasia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13287-026-05086-2","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:20:31Z","timestamp":1788528031000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intravenously delivered multilineage-differentiating stress-enduring cells dampen hyperoxia-induced lung injury in a rat model with features of bronchopulmonary dysplasia"],"prefix":"10.1186","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9198-9076","authenticated-orcid":false,"given":"Ryosuke","family":"Miura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4923-062X","authenticated-orcid":false,"given":"Atsuto","family":"Onoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azusa","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8760-1404","authenticated-orcid":false,"given":"Toshihiko","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Kanzawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2114-9499","authenticated-orcid":false,"given":"Sakiko","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuto","family":"Ueda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9066-3489","authenticated-orcid":false,"given":"Shinobu","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Hayakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6320-9176","authenticated-orcid":false,"given":"Yoshiaki","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"5086_CR1","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.rmed.2017.10.014","volume":"132","author":"R Kalikkot Thekkeveedu","year":"2017","unstructured":"Kalikkot Thekkeveedu R, Guaman MC, Shivanna B. 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The title of the approved project was \u201cEstablishment of a neonatal rat model of BPD and development of novel therapeutic strategies\u201d, and the dates of approval were March 18, 2014 (No. 26126), March 16, 2015 (No. 27190), March 11, 2016 (No. 28215), March 10, 2017 (No. 29012), March 19, 2018 (No. 30197), March 8, 2019 (No. 31106), March 6, 2020 (No. 20032), March 3, 2021 (No. M210107-003). Human BM-MSCs were purchased from Lonza. According to the manufacturer\u2019s documentation and published information, Lonza obtained ethical approval for the collection of human bone marrow samples, and written informed consent was obtained from all donors (Supplemental Material 1, 2).","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and\/or publication of this article: Y.S. and S.Sh have a collaborative research and developmental agreement for perinatal disease with Life Science Institute Inc. (LSII). S.Sh is making a collaborative research and developmental agreement for the other disease, and has a contract for consulting with LSII. Y.S., T.S and S.Sh have a patent for the application of Muse cells for treatment of perinatal brain damage and the other indication. R.M, A.On, A.Ok, S.Su, K.U, Y.T and M.H declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"300"}}