{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T08:31:00Z","timestamp":1769589060734,"version":"3.49.0"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Acute respiratory distress syndrome (ARDS) prevention in patients coincide with significant risk factors, including severe sepsis. Cardiosphere-derived cells (CDCs) are cardiac stromal\/progenitor cells with anti-inflammatory and immunomodulatory effects, which may impact favorably on sepsis-induced acute lung injury (ALI). We used a pig model of sepsis (lipopolysaccharide, LPS) to test whether CDCs, given IV in a preventive paradigm, can ameliorate ALI, relative to placebo. Yorkshire\/Landrace hybrid domestic pigs (n\u2009=\u200934) were divided into 3 groups: 1) healthy controls; 2) LPS (60ug\/kg) + saline (placebo) group; and 3) LPS\u2009+\u2009CDC group, with CDCs given in 3 different doses (25, 50 and 100 million cells) after LPS. All pigs were briefly intubated on mechanical ventilation on room air to obtain baseline and 1-hour data and again at the final endpoint of 48hours. Chest mechanics, gas exchange, hemodynamics, blood, bronchoalveolar lavage assays and lung histology were assessed. LPS\u2009+\u2009CDCs compared with LPS\u2009+\u2009saline improved: gas exchange (increased hypoxemia ratio [p\u2009=\u20090.03],chest mechanics (respiratory compliance [p\u2009=\u20090.002]; peak and plateau pressures [p\u2009=\u20090.01\/0.049]), pulmonary hemodynamics (decreased pulmonary artery pressures [p\u2009=\u2009.0008]), reduced BAL neutrophils [p\u2009=\u20090.04]), and systemic cytokines, e.g., IL-1, IL-6, IL-18 and IFN\u03b3 [p\u2009&lt;\u20090.05]) and serum creatinine (p\u2009=\u20090.02), while alveolar lavage cytokines, e.g., IL-1, IL-6,IL-8,and IL-18 were changed. Histopathology was improved (decreased atelectasis, hemorrhage and arteriolar thickness). In summary, CDCs given in a preventive fashion, attenuated manifestations of LPS-induced ALI. As CDCs have an extensive safety record in hundreds of patients, our findings motivate clinical testing of CDCs for the primary prevention of sepsis-induced ARDS.<\/jats:p>","DOI":"10.1371\/journal.pone.0338336","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T18:36:06Z","timestamp":1769538966000},"page":"e0338336","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiosphere-derived cells in the primary prevention of sepsis-induced acute lung injury in pigs"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2387-1488","authenticated-orcid":true,"given":"James Frederick","family":"Dawkins","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asma","family":"Nawaz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lizbeth","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1764-182X","authenticated-orcid":true,"given":"Ralf","family":"Sulague","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiyana","family":"Verfaillie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Cardenas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenio","family":"Cingolani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Marb\u00e1n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"pone.0338336.ref001","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1164\/ajrccm.151.2.7842182","article-title":"Clinical risks for development of the acute respiratory distress syndrome","volume":"151","author":"LD Hudson","year":"1995","journal-title":"Am J Respir Crit Care Med"},{"key":"pone.0338336.ref002","doi-asserted-by":"crossref","DOI":"10.1097\/01.CCM.0000145947.19077.25","article-title":"Mechanical ventilation in sepsis-induced acute lung injury\/acute respiratory distress syndrome: an evidence-based review","volume":"32","author":"JE Sevransky","year":"2004","journal-title":"Crit Care Med"},{"issue":"16","key":"pone.0338336.ref003","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1056\/NEJMoa050333","article-title":"Incidence and outcomes of acute lung injury","volume":"353","author":"GD Rubenfeld","year":"2005","journal-title":"N Engl J Med"},{"issue":"3","key":"pone.0338336.ref004","article-title":"The Epidemiology of Sepsis in Chinese ICUs: A National Cross-Sectional Survey","volume":"48","author":"J Xie","year":"2020","journal-title":"Crit Care Med"},{"issue":"10300","key":"pone.0338336.ref005","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/S0140-6736(21)00439-6","article-title":"Acute respiratory distress syndrome","volume":"398","author":"NJ Meyer","year":"2021","journal-title":"Lancet"},{"issue":"6","key":"pone.0338336.ref006","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1164\/rccm.201609-1767CI","article-title":"Fifty Years of Research in ARDS. 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