{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T21:49:24Z","timestamp":1776721764933,"version":"3.51.2"},"reference-count":76,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007408","name":"Medical Center, University of Pittsburgh","doi-asserted-by":"publisher","award":["I00000171"],"award-info":[{"award-number":["I00000171"]}],"id":[{"id":"10.13039\/100007408","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["CTN01_00177_888744"],"award-info":[{"award-number":["CTN01_00177_888744"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The clinical results of lung transplantation (LTx) are still less favorable than other solid organ transplants in both the early and long term. The fragility of the lungs limits the procurement rate and can favor the occurrence of ischemia-reperfusion injury (IRI). Ex vivo lung perfusion (EVLP) with Steen SolutionTM (SS) aims to address problems, and the implementation of EVLP to alleviate the activation of IRI-mediated processes has been achieved using mesenchymal stromal\/stem cell (MSC)-based treatments. In this study, we investigated the paracrine effects of human amnion-derived MSCs (hAMSCs) in an in vitro model of lung IRI that includes cold ischemia and normothermic EVLP. We found that SS enriched by a hAMSC-conditioned medium (hAMSC-CM) preserved the viability and delayed the apoptosis of alveolar epithelial cells (A549) through the downregulation of inflammatory factors and the upregulation of antiapoptotic factors. These effects were more evident using the CM of 3D hAMSC cultures, which contained an increased amount of immunosuppressive and growth factors compared to both 2D cultures and encapsulated-hAMSCs. To conclude, we demonstrated an in vitro model of lung IRI and provided evidence that a hAMSC-CM attenuated IRI effects by improving the efficacy of EVLP, leading to strategies for a potential implementation of this technique.<\/jats:p>","DOI":"10.3390\/ijms22020510","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T20:45:42Z","timestamp":1609965942000},"page":"510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Conditioned Medium from Human Amnion-Derived Mesenchymal Stromal\/Stem Cells Attenuating the Effects of Cold Ischemia-Reperfusion Injury in an In Vitro Model Using Human Alveolar Epithelial Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8922-9909","authenticated-orcid":false,"given":"Vitale","family":"Miceli","sequence":"first","affiliation":[{"name":"Research Department, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Bertani","sequence":"additional","affiliation":[{"name":"Thoracic Surgery and Lung Transplantation Unit, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9318-6606","authenticated-orcid":false,"given":"Cinzia Maria","family":"Chinnici","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Unit, Fondazione Ri.MED, 90127 Palermo, Italy"},{"name":"Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS\u2013ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Bulati","sequence":"additional","affiliation":[{"name":"Research Department, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariangela","family":"Pampalone","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Unit, Fondazione Ri.MED, 90127 Palermo, Italy"},{"name":"Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS\u2013ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6957-9861","authenticated-orcid":false,"given":"Giandomenico","family":"Amico","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Unit, Fondazione Ri.MED, 90127 Palermo, Italy"},{"name":"Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS\u2013ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0305-1781","authenticated-orcid":false,"given":"Claudia","family":"Carcione","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Unit, Fondazione Ri.MED, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Schmelzer","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219-3130, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg C.","family":"Gerlach","sequence":"additional","affiliation":[{"name":"Department of Surgery, School of Medicine, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219-3130, USA"},{"name":"Department of Bioengineering, School of Medicine, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219-3130, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pier Giulio","family":"Conaldi","sequence":"additional","affiliation":[{"name":"Research Department, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.21037\/jtd.2017.07.85","article-title":"Outcomes after lung transplantation","volume":"9","author":"Thabut","year":"2017","journal-title":"J. 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