{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:57:01Z","timestamp":1787579821804,"version":"build-2736575974"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Peer Reviewed Medical Research Program","award":["W81XWH-13-2-0005"],"award-info":[{"award-number":["W81XWH-13-2-0005"]}]},{"name":"Peer Reviewed Medical Research Program","award":["W81XWH-13-2-0005"],"award-info":[{"award-number":["W81XWH-13-2-0005"]}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Early post injury mitigation strategies in ARDS are in short supply. Treatments with allogeneic stromal cells are administered after ARDS develops, require specialized expertise and equipment, and to date have shown limited benefit.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Assess the efficacy of immediate post injury intravenous administration of autologous or allogeneic bone marrow\u2013derived mesenchymal stromal cells (MSCs) for the treatment of acute respiratory distress syndrome (ARDS) due to smoke inhalation and burns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Yorkshire swine (n\u2009=\u200932, 44.3\u2009\u00b1\u20090.5\u2009kg) underwent intravenous anesthesia, placement of lines, severe smoke inhalation, and 40% total body surface area flame burns, followed by 72\u2009hours of around-the-clock ICU care. Mechanical ventilation, fluids, pressors, bronchoscopic cast removal, daily lung computed tomography scans, and arterial blood assays were performed. After injury and 24 and 48\u2009hours later, animals were randomized to receive autologous concentrated bone marrow aspirate (n\u2009=\u200910; 3\u2009\u00d7\u2009106 white blood cells and a mean of 56.6\u2009\u00d7\u2009106 platelets per dose), allogeneic MSCs (n\u2009=\u200910; 6.1\u2009\u00d7\u2009106 MSCs per dose) harvested from healthy donor swine, or no treatment in injured control animals (n\u2009=\u200912).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>The intravenous administration of MSCs after injury and at 24 and 48\u2009hours delayed the onset of ARDS in swine treated with autologous MSCs (48\u2009\u00b1\u200910\u2009h) versus control animals (14\u2009\u00b1\u20092\u2009h) (P\u2009=\u20090.004), reduced ARDS severity at 24 (P\u2009&amp;lt;\u20090.001) and 48 (P\u2009=\u20090.003) hours, and demonstrated visibly diminished consolidation on computed tomography (not significant). Mortality at 72\u2009hours was 1 in 10 (10%) in the autologous group, 5 in 10 (50%) in the allogeneic group, and 6 in 12 (50%) in injured control animals (not significant). Both autologous and allogeneic MSCs suppressed systemic concentrations of TNF-\u03b1 (tumor necrosis factor-\u03b1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The intravenous administration of three doses of freshly processed autologous bone marrow\u2013derived MSCs delays ARDS development and reduces its severity in swine. Bedside retrieval and administration of autologous MSCs in swine is feasible and may be a viable injury mitigation strategy for ARDS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202305-0865oc","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T14:54:37Z","timestamp":1696517677000},"page":"1283-1292","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":12,"title":["Intravenous Autologous Bone Marrow\u2013derived Mesenchymal Stromal Cells Delay Acute Respiratory Distress Syndrome in Swine"],"prefix":"10.1093","volume":"208","author":[{"given":"Andriy I.","family":"Batchinsky","sequence":"first","affiliation":[{"name":"Autonomous Reanimation and Evacuation Research Program, The Geneva Foundation, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teryn R.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Autonomous Reanimation and Evacuation Research Program, The Geneva Foundation, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Antebi","sequence":"additional","affiliation":[{"name":"Maryland Stem Cell Research Fund, Columbia, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corina","family":"Necsoiu","sequence":"additional","affiliation":[{"name":"U.S. Army Institute of Surgical Research, Joint Base San Antonio Fort Sam Houston, Fort Sam Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae H.","family":"Choi","sequence":"additional","affiliation":[{"name":"59th Medical Wing, Joint Base San Antonio Lackland Air Force Base, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryanne","family":"Herzig","sequence":"additional","affiliation":[{"name":"U.S. Army Institute of Surgical Research, Joint Base San Antonio Fort Sam Houston, Fort Sam Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Cap","sequence":"additional","affiliation":[{"name":"U.S. Army Institute of Surgical Research, Joint Base San Antonio Fort Sam Houston, Fort Sam Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S.","family":"McDaniel","sequence":"additional","affiliation":[{"name":"59th Medical Wing, Joint Base San Antonio Lackland Air Force Base, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Rathbone","sequence":"additional","affiliation":[{"name":"University of Texas at San Antonio, San Antonio, Texas; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin K.","family":"Chung","sequence":"additional","affiliation":[{"name":"SeaStar Medical, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leopoldo C.","family":"Cancio","sequence":"additional","affiliation":[{"name":"U.S. Army Institute of Surgical Research, Joint Base San Antonio Fort Sam Houston, Fort Sam Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,15]]},"reference":[{"key":"2026012204401148500_bib1","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1097\/TA.0b013e3182aa2d21","article-title":"Acute respiratory distress syndrome in wartime military burns: application of the Berlin criteria","volume":"76","author":"Belenkiy","year":"2014","journal-title":"J Trauma Acute Care Surg"},{"key":"2026012204401148500_bib2","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1080\/17476348.2020.1804365","article-title":"Mortality in COVID-19 patients with acute respiratory distress syndrome and corticosteroids use: a systematic review and meta-analysis","volume":"14","author":"Hasan","year":"2020","journal-title":"Expert Rev Respir Med"},{"key":"2026012204401148500_bib3","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1164\/rccm.201701-0107CP","article-title":"Fifty years of research in ARDS: cell-based therapy for acute respiratory distress syndrome. Biology and potential therapeutic value","volume":"196","author":"Laffey","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204401148500_bib4","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1001\/jama.2020.6775","article-title":"Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area","volume":"323","author":"Richardson","year":"2020","journal-title":"JAMA"},{"key":"2026012204401148500_bib5","doi-asserted-by":"crossref","first-page":"S276","DOI":"10.1097\/01.CCM.0000057904.62683.2B","article-title":"Epidemiology of acute lung injury","volume":"31","author":"Rubenfeld","year":"2003","journal-title":"Crit Care Med"},{"key":"2026012204401148500_bib6","first-page":"2526","article-title":"Acute respiratory distress syndrome: the Berlin definition","volume":"307","author":"Ranieri","year":"2012","journal-title":"JAMA"},{"key":"2026012204401148500_bib7","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s001340050529","article-title":"From ventilator-induced lung injury to multiple organ dysfunction?","volume":"24","author":"Dreyfuss","year":"1998","journal-title":"Intensive Care Med"},{"key":"2026012204401148500_bib8","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1056\/NEJM200005043421801","article-title":"Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome","volume":"342","author":"Brower","year":"2000","journal-title":"N Engl J Med"},{"key":"2026012204401148500_bib9","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1056\/NEJM199802053380602","article-title":"Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome","volume":"338","author":"Amato","year":"1998","journal-title":"N Engl J Med"},{"key":"2026012204401148500_bib10","doi-asserted-by":"crossref","first-page":"2314","DOI":"10.1097\/CCM.0b013e318225b5b3","article-title":"Comparison of airway pressure release ventilation to conventional mechanical ventilation in the early management of smoke inhalation injury in swine","volume":"39","author":"Batchinsky","year":"2011","journal-title":"Crit Care Med"},{"key":"2026012204401148500_bib11","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1097\/TA.0000000000001713","article-title":"The promise of mesenchymal stem cell therapy for acute respiratory distress syndrome","volume":"84","author":"Antebi","year":"2018","journal-title":"J Trauma Acute Care Surg"},{"key":"2026012204401148500_bib12","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1186\/s13287-018-0981-3","article-title":"The effect of acute respiratory distress syndrome on bone marrow-derived mesenchymal stem cells","volume":"9","author":"Antebi","year":"2018","journal-title":"Stem Cell Res Ther"},{"key":"2026012204401148500_bib13","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1002\/sctm.18-0236","article-title":"Mesenchymal stem cells reconditioned in their own serum exhibit augmented therapeutic properties in the setting of acute respiratory distress syndrome","volume":"8","author":"Xu","year":"2019","journal-title":"Stem Cells Transl Med"},{"key":"2026012204401148500_bib14","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1111\/j.1440-1843.2010.01829.x","article-title":"High MW hyaluronan inhibits smoke inhalation-induced lung injury and improves survival","volume":"15","author":"Huang","year":"2010","journal-title":"Respirology"},{"key":"2026012204401148500_bib15","doi-asserted-by":"crossref","first-page":"e0185937","DOI":"10.1371\/journal.pone.0185937","article-title":"Adipose-derived stem cells attenuate pulmonary microvascular hyperpermeability after smoke inhalation","volume":"12","author":"Ihara","year":"2017","journal-title":"PLoS One"},{"key":"2026012204401148500_bib16","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/S2213-2600(18)30418-1","article-title":"Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial","volume":"7","author":"Matthay","year":"2019","journal-title":"Lancet Respir Med"},{"key":"2026012204401148500_bib17","doi-asserted-by":"crossref","first-page":"S569","DOI":"10.1097\/CCM.0b013e3181f1ff1d","article-title":"Mesenchymal stem cells for acute lung injury: preclinical evidence","volume":"38","author":"Matthay","year":"2010","journal-title":"Crit Care Med"},{"key":"2026012204401148500_bib18","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s12967-020-02300-4","article-title":"Emerging therapies for smoke inhalation injury: a review","volume":"18","author":"Mercel","year":"2020","journal-title":"J Transl Med"},{"key":"2026012204401148500_bib19","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1165\/rcmb.2004-0330OC","article-title":"Bone marrow-derived mesenchymal stem cells in repair of the injured lung","volume":"33","author":"Rojas","year":"2005","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026012204401148500_bib20","first-page":"224","article-title":"Effects of bone marrow-derived mesenchymal stem cells engraftment on vascular endothelial cell growth factor in lung tissue and plasma at early stage of smoke inhalation injury","volume":"1","author":"Zhu","year":"2010","journal-title":"World J Emerg Med"},{"key":"2026012204401148500_bib21","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1164\/rccm.202201-0157OC","article-title":"A randomized trial of mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome from COVID-19","volume":"207","author":"Bowdish","year":"2023","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204401148500_bib22","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1164\/rccm.202003-0544LE","article-title":"Five-year follow-up after mesenchymal stromal cell-based treatment of severe acute respiratory distress syndrome","volume":"202","author":"Simonson","year":"2020","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204401148500_bib23","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.3389\/fimmu.2020.01091","article-title":"MSC therapies for COVID-19: importance of patient coagulopathy, thromboprophylaxis, cell product quality and mode of delivery for treatment safety and efficacy","volume":"11","author":"Moll","year":"2020","journal-title":"Front Immunol"},{"key":"2026012204401148500_bib24","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1164\/rccm.201303-0522WS","article-title":"Cell therapy for lung diseases: report from an NIH-NHLBI workshop, November 13\u201314, 2012","volume":"188","author":"Matthay","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204401148500_bib25","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/scrt430","article-title":"Human adult bone marrow-derived stem cells decrease severity of lipopolysaccharide-induced acute respiratory distress syndrome in sheep","volume":"5","author":"Rojas","year":"2014","journal-title":"Stem Cell Res Ther"},{"key":"2026012204401148500_bib26","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1136\/thoraxjnl-2013-204980","article-title":"Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia","volume":"69","author":"Asmussen","year":"2014","journal-title":"Thorax"},{"key":"2026012204401148500_bib27","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1097\/SHK.0000000000000177","article-title":"The noninvasive carbon dioxide gradient (NICO2G) during hemorrhagic shock","volume":"42","author":"Belenkiy","year":"2014","journal-title":"Shock"},{"key":"2026012204401148500_bib28","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1016\/j.burns.2019.07.020","article-title":"Effects of adjunct treatments on end-organ damage and histological injury severity in acute respiratory distress syndrome and multiorgan failure caused by smoke inhalation injury and burns","volume":"45","author":"Choi","year":"2019","journal-title":"Burns"},{"key":"2026012204401148500_bib29","author":"Batchinsky","year":"2018"},{"key":"2026012204401148500_bib30","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1097\/01.ta.0000205862.57701.48","article-title":"Acute respiratory distress syndrome secondary to inhalation of chlorine gas in sheep","volume":"60","author":"Batchinsky","year":"2006","journal-title":"J Trauma"},{"key":"2026012204401148500_bib31","doi-asserted-by":"crossref","first-page":"e211","DOI":"10.1097\/CCM.0000000000000121","article-title":"Extracorporeal gas exchange and spontaneous breathing for the treatment of acute respiratory distress syndrome: an alternative to mechanical ventilation?","volume":"42","author":"Langer","year":"2014","journal-title":"Crit Care Med"},{"key":"2026012204401148500_bib32","doi-asserted-by":"crossref","first-page":"1836960","DOI":"10.1155\/2017\/1836960","article-title":"Quantitative assessment of optimal bone marrow site for the isolation of porcine mesenchymal stem cells","volume":"2017","author":"McDaniel","year":"2017","journal-title":"Stem Cells Int"},{"key":"2026012204401148500_bib33","doi-asserted-by":"crossref","first-page":"279","DOI":"10.2217\/rme-2018-0043","article-title":"Bench-to-bedside optimization of mesenchymal stem cell isolation, processing, and expansion for in vivo administration","volume":"14","author":"Antebi","year":"2019","journal-title":"Regen Med"},{"key":"2026012204401148500_bib34","doi-asserted-by":"crossref","first-page":"462","DOI":"10.3390\/cells8050462","article-title":"Preconditioning in an inflammatory milieu augments the immunotherapeutic function of mesenchymal stromal cells","volume":"8","author":"Rodriguez","year":"2019","journal-title":"Cells"},{"key":"2026012204401148500_bib35","doi-asserted-by":"crossref","first-page":"107694","DOI":"10.1016\/j.intimp.2021.107694","article-title":"Mesenchymal stromal\/stem cells (MSCs) and MSC-derived extracellular vesicles in COVID-19\u2013induced ARDS: mechanisms of action, research progress, challenges, and opportunities","volume":"97","author":"Moradinasab","year":"2021","journal-title":"Int Immunopharmacol"},{"key":"2026012204401148500_bib36","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1128\/MMBR.05015-11","article-title":"Into the eye of the cytokine storm","volume":"76","author":"Tisoncik","year":"2012","journal-title":"Microbiol Mol Biol Rev"},{"key":"2026012204401148500_bib37","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1186\/s13287-020-01804-6","article-title":"Mesenchymal stem cells: current clinical progress in ARDS and COVID-19","volume":"11","author":"Xiao","year":"2020","journal-title":"Stem Cell Res Ther"},{"key":"2026012204401148500_bib38","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13287-018-0774-8","article-title":"Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig model","volume":"9","author":"Khatri","year":"2018","journal-title":"Stem Cell Res Ther"},{"key":"2026012204401148500_bib39","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s13287-021-02165-4","article-title":"Mesenchymal stem cells derived from perinatal tissues for treatment of critically ill COVID-19-induced ARDS patients: a case series","volume":"12","author":"Hashemian","year":"2021","journal-title":"Stem Cell Res Ther"},{"key":"2026012204401148500_bib40","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1097\/CCM.0b013e3181eb9d0b","article-title":"High-frequency percussive ventilation and low tidal volume ventilation in burns: a randomized controlled trial","volume":"38","author":"Chung","year":"2010","journal-title":"Crit Care Med"},{"key":"2026012204401148500_bib41","first-page":"9427978","article-title":"The effect of intravenous autologous activated platelet-rich plasma therapy on \u201cprofibrotic cytokine\u201d IL-1\u03b2 levels in severe and critical COVID-19 patients: a preliminary study","volume":"2021","author":"Karina","year":"2021","journal-title":"Scientifica (Cairo)"},{"key":"2026012204401148500_bib42","first-page":"e33265","article-title":"Platelet-rich plasma treatment for chronic respiratory disease","volume":"15","author":"Knight","year":"2023","journal-title":"Cureus"},{"key":"2026012204401148500_bib43","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1165\/rcmb.2014-0076OC","article-title":"Platelet-rich plasma extract prevents pulmonary edema through angiopoietin-Tie2 signaling","volume":"52","author":"Mammoto","year":"2015","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026012204401148500_bib44","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.3349\/ymj.2013.54.5.1293","article-title":"Familial occurrence of pulmonary embolism after intravenous, adipose tissue-derived stem cell therapy","volume":"54","author":"Jung","year":"2013","journal-title":"Yonsei Med J"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/208\/12\/1283\/66425199\/ajrccm_208_12_1283.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/208\/12\/1283\/66425199\/ajrccm_208_12_1283.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T09:40:23Z","timestamp":1769074823000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/208\/12\/1283\/8426853"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12]]},"references-count":44,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12,15]]},"published-print":{"date-parts":[[2023,12,15]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.202305-0865oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,12]]},"published":{"date-parts":[[2023,12]]},"assertion":[{"value":"2023-05-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}