{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:04:37Z","timestamp":1792123477904,"version":"4.4.0"},"reference-count":40,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T00:00:00Z","timestamp":1678665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"VA Merit Review","award":["I01 BX000760 (RFK)"],"award-info":[{"award-number":["I01 BX000760 (RFK)"]}]},{"name":"VA Merit Review","award":["I01 BX004146 (TAB)"],"award-info":[{"award-number":["I01 BX004146 (TAB)"]}]},{"name":"United States (U.S.) Department of Veterans Affairs BLR&amp;D","award":["I01 BX000760 (RFK)"],"award-info":[{"award-number":["I01 BX000760 (RFK)"]}]},{"name":"United States (U.S.) Department of Veterans Affairs BLR&amp;D","award":["I01 BX004146 (TAB)"],"award-info":[{"award-number":["I01 BX004146 (TAB)"]}]},{"name":"University of Minnesota Lillehei Heart Institute","award":["I01 BX000760 (RFK)"],"award-info":[{"award-number":["I01 BX000760 (RFK)"]}]},{"name":"University of Minnesota Lillehei Heart Institute","award":["I01 BX004146 (TAB)"],"award-info":[{"award-number":["I01 BX004146 (TAB)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diastolic dysfunction persists despite coronary artery bypass graft surgery (CABG) in patients with hibernating myocardium (HIB). We studied whether the adjunctive use of a mesenchymal stem cells (MSCs) patch during CABG improves diastolic function by reducing inflammation and fibrosis. HIB was induced in juvenile swine by placing a constrictor on the left anterior descending (LAD) artery, causing myocardial ischemia without infarction. At 12 weeks, CABG was performed using the left-internal-mammary-artery (LIMA)-to-LAD graft with or without placement of an epicardial vicryl patch embedded with MSCs, followed by four weeks of recovery. The animals underwent cardiac magnetic resonance imaging (MRI) prior to sacrifice, and tissue from septal and LAD regions were collected to assess for fibrosis and analyze mitochondrial and nuclear isolates. During low-dose dobutamine infusion, diastolic function was significantly reduced in HIB compared to the control, with significant improvement after CABG + MSC treatment. In HIB, we observed increased inflammation and fibrosis without transmural scarring, along with decreased peroxisome proliferator-activated receptor-gamma coactivator (PGC1\u03b1), which could be a possible mechanism underlying diastolic dysfunction. Improvement in PGC1\u03b1 and diastolic function was noted with revascularization and MSCs, along with decreased inflammatory signaling and fibrosis. These findings suggest that adjuvant cell-based therapy during CABG may recover diastolic function by reducing oxidant stress\u2013inflammatory signaling and myofibroblast presence in the myocardial tissue.<\/jats:p>","DOI":"10.3390\/ijms24065475","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T03:04:46Z","timestamp":1678763086000},"page":"5475","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["An Adjuvant Stem Cell Patch with Coronary Artery Bypass Graft Surgery Improves Diastolic Recovery in Porcine Hibernating Myocardium"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5337-4837","authenticated-orcid":false,"given":"Rishav","family":"Aggarwal","sequence":"first","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koray N.","family":"Potel","sequence":"additional","affiliation":[{"name":"School of Medicine, Dentistry and Biomedical Sciences, Queen\u2019s University Belfast, Belfast BT9 7BL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Shao","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7409-073X","authenticated-orcid":false,"given":"Simon W.","family":"So","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Department of Research, Center for Veterans Research and Education, Minneapolis, MN 55417, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory","family":"Swingen","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina P.","family":"Reyes","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Rose","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christin","family":"Wright","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura L.","family":"Hocum Stone","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward O.","family":"McFalls","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Richmond VA Medical Center, Richmond, VA 23249, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy A.","family":"Butterick","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Department of Research, Center for Veterans Research and Education, Minneapolis, MN 55417, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary F.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1056\/NEJMoa1100356","article-title":"Coronary-Artery Bypass Surgery in Patients with Left Ventricular Dysfunction","volume":"364","author":"Velazquez","year":"2011","journal-title":"N. 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