{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:27:48Z","timestamp":1790782068268,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,9,30]],"date-time":"2018-09-30T00:00:00Z","timestamp":1538265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002081","name":"Irish Research Council","doi-asserted-by":"publisher","award":["GOIPG\/2015\/1818"],"award-info":[{"award-number":["GOIPG\/2015\/1818"]}],"id":[{"id":"10.13039\/501100002081","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alveolar epithelial dysfunction induced by hypoxic stress plays a significant role in the pathological process of lung ischemia-reperfusion injury (IRI). Mesenchymal stem cell (MSC) therapies have demonstrated efficacy in exerting protective immunomodulatory effects, thereby reducing airway inflammation in several pulmonary diseases. Aim: This study assesses the protective effects of MSC secretome from different cell sources, human bone marrow (BMSC) and adipose tissue (ADSC), in attenuating hypoxia-induced cellular stress and inflammation in pulmonary epithelial cells. Methods: Pulmonary epithelial cells, primary rat alveolar epithelial cells (AEC) and A549 cell line were pre-treated with BMSC, or ADSC conditioned medium (CM) and subjected to hypoxia for 24 h. Results: Both MSC-CM improved cell viability, reduced secretion of pro-inflammatory mediators and enhanced IL-10 anti-inflammatory cytokine production in hypoxic injured primary rat AECs. ADSC-CM reduced hypoxic cellular injury by mechanisms which include: inhibition of p38 MAPK phosphorylation and nuclear translocation of subunits in primary AECs. Both MSC-CM enhanced translocation of Bcl-2 to the nucleus, expression of cytoprotective glucose-regulated proteins (GRP) and restored matrix metalloproteinases (MMP) function, thereby promoting repair and cellular homeostasis, whereas inhibition of GRP chaperones was detrimental to cell survival. Conclusions: Elucidation of the protective mechanisms exerted by the MSC secretome is an essential step for maximizing the therapeutic effects, in addition to developing therapeutic targets-specific strategies for various pulmonary syndromes.<\/jats:p>","DOI":"10.3390\/ijms19102996","type":"journal-article","created":{"date-parts":[[2018,10,2]],"date-time":"2018-10-02T08:23:50Z","timestamp":1538468630000},"page":"2996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Human Mesenchymal Stem Cell Secretome from Bone Marrow or Adipose-Derived Tissue Sources for Treatment of Hypoxia-Induced Pulmonary Epithelial Injury"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7298-2870","authenticated-orcid":false,"given":"Nala","family":"Shologu","sequence":"first","affiliation":[{"name":"The Discipline of Anesthesia and Lung Biology Group, National University of Ireland Galway, H91 TK33 Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Scully","sequence":"additional","affiliation":[{"name":"Critical Care Medicine and Intensive Care, University Hospital Galway, H91 YR71 Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Laffey","sequence":"additional","affiliation":[{"name":"The Discipline of Anesthesia and Lung Biology Group, National University of Ireland Galway, H91 TK33 Galway, Ireland"},{"name":"Critical Care Medicine and Intensive Care, University Hospital Galway, H91 YR71 Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"O\u2019Toole","sequence":"additional","affiliation":[{"name":"The Discipline of Anesthesia and Lung Biology Group, National University of Ireland Galway, H91 TK33 Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1002\/jcb.24783","article-title":"Mesenchymal stem cell trials for pulmonary diseases","volume":"115","author":"Antunes","year":"2014","journal-title":"J. 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