{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:51:40Z","timestamp":1791399100994,"version":"4.3.3"},"reference-count":68,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Heart-in-a-Dish","award":["CGS-M"],"award-info":[{"award-number":["CGS-M"]}]},{"name":"Courtois Cardiovascular Signature Program","award":["CGS-M"],"award-info":[{"award-number":["CGS-M"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["CGS-M"],"award-info":[{"award-number":["CGS-M"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>During a heart attack, ischemia causes losses of billions of cells; this is especially concerning given the minimal regenerative capability of cardiomyocytes (CMs). Heart remuscularization utilizing stem cells has improved cardiac outcomes despite little cell engraftment, thereby shifting focus to cell-free therapies. Consequently, we chose induced pluripotent stem cells (iPSCs) given their pluripotent nature, efficacy in previous studies, and easy obtainability from minimally invasive techniques. Nonetheless, using iPSC secretome-based therapies for treating injured CMs in a clinical setting is ill-understood. We hypothesized that the iPSC secretome, regardless of donor health, would improve cardiovascular outcomes in the CM model of ischemia\u2013reperfusion (IR) injury. Episomal-generated iPSCs from healthy and dilated cardiomyopathy (DCM) donors, passaged 6\u201310 times, underwent 24 h incubation in serum-free media. Protein content of the secretome was analyzed by mass spectroscopy and used to treat AC16 immortalized CMs during 5 h reperfusion following 24 h of hypoxia. IPSC-derived secretome content, independent of donor health status, had elevated expression of proteins involved in cell survival pathways. In IR conditions, iPSC-derived secretome increased cell survival as measured by metabolic activity (p &lt; 0.05), cell viability (p &lt; 0.001), and maladaptive cellular remodelling (p = 0.052). Healthy donor-derived secretome contained increased expression of proteins related to calcium contractility compared to DCM donors. Congruently, only healthy donor-derived secretomes improved CM intracellular calcium concentrations (p &lt; 0.01). Heretofore, secretome studies mainly investigated differences relating to cell type rather than donor health. Our work suggests that healthy donors provide more efficacious iPSC-derived secretome compared to DCM donors in the context of IR injury in human CMs. These findings illustrate that the regenerative potential of the iPSC secretome varies due to donor-specific differences.<\/jats:p>","DOI":"10.3390\/ijms251910279","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T10:41:47Z","timestamp":1727174507000},"page":"10279","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Evaluating the Reparative Potential of Secretome from Patient-Derived Induced Pluripotent Stem Cells during Ischemia\u2013Reperfusion Injury in Human Cardiomyocytes"],"prefix":"10.3390","volume":"25","author":[{"given":"Elise","family":"Rody","sequence":"first","affiliation":[{"name":"Department of Surgery, Division of Cardiac Surgery, McGill University Health Center, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7382-9253","authenticated-orcid":false,"given":"Jeremy","family":"Zwaig","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, McGill University, Montreal, QC H3G 2M1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Derish","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, McGill University, Montreal, QC H3G 2M1, Canada"},{"name":"Department of Surgical and Interventional Sciences, McGill University, Montreal, QC H3G 1A4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3974-5136","authenticated-orcid":false,"given":"Kashif","family":"Khan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, McGill University, Montreal, QC H3G 2M1, Canada"},{"name":"Department of Medicine, Division of Cardiology, McGill University Health Center, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadezda","family":"Kachurina","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, McGill University Health Center, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Gendron","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, McGill University Health Center, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Giannetti","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, McGill University Health Center, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5820-0775","authenticated-orcid":false,"given":"Adel","family":"Schwertani","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, McGill University Health Center, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2611-3698","authenticated-orcid":false,"given":"Renzo","family":"Cecere","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Cardiac Surgery, McGill University Health Center, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/7651_2015_225","article-title":"Skin Biopsy and Patient-Specific Stem Cell Lines","volume":"1353","author":"Li","year":"2016","journal-title":"Methods Mol. 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