Objective: This study aims to investigate the utility of mesenchymal stem cells (MSCs) applied as an epicardial patch during coronary artery bypass graft (CABG) to target hibernating myocardium; that is, tissue with persistently decreased myocardial function, in a large animal model. Methods: Hibernating myocardium was induced in juvenile swine (n = 12) using a surgically placed constrictor on the left anterior descending artery, causing stenosis without infarction. After 12 weeks, single-vessel CABG was performed using left internal thoracic artery to left anterior descending artery graft. During CABG, an epicardial patch was applied to the hibernating myocardium region consisting either of MSCs grown onto a polyglactin mesh (n = 6), or sham polyglactin mesh without MSCs (n = 6). Four weeks after CABG and patch placement, cardiac magnetic resonance imaging was performed and cardiac tissue was examined by gross inspection, including coronary dilators for vessel stenosis and patency, electron microscopy, protein assays, and proteomic analysis. Results: CABG + MSC myocardium showed improvement in contractile function (78.24% ± 19.6%) compared with sham patch (39.17% ± 5.57%) during inotropic stimulation (P < .05). Compared with sham patch control, electron microscopy of CABG + MSC myocardium showed improvement in mitochondrial size, number, and morphology; protein analysis similarly showed increases in expression of the mitochondrial biogenesis marker peroxisome proliferator-activated receptor gamma coactivator 1-alpha (0.0022 ± 0.0009 vs 0.023 ± 0.009) (P < .01) along with key components of the electron transport chain, including succinate dehydrogenase (complex II) (0.06 ± 0.02 vs 0.14 ± 0.03) (P < .05) and adenosine triphosphate synthase (complex V) (2.7 ± 0.4 vs 4.2 ± 0.26) (P < .05). Conclusions: In hibernating myocardium, placement of a stem cell patch during CABG shows promise in improving myocardial function by improving mitochondrial morphology and function.
Bibliographical noteFunding Information:
Supported by VA Merit Review #I01 BX000760 to Dr Kelly from the US Department of Veterans Affairs Biomedical Laboratory Research & Development and the Lillehei Heart Institute at the University of Minnesota . The contents of this work do not represent the views of the US Department of Veterans Affairs of the US Government.
Supported by VA Merit Review #I01 BX000760 to Dr Kelly from the US Department of Veterans Affairs Biomedical Laboratory Research & Development and the Lillehei Heart Institute at the University of Minnesota. The contents of this work do not represent the views of the US Department of Veterans Affairs of the US Government.
© 2020 The American Association for Thoracic Surgery
Copyright 2020 Elsevier B.V., All rights reserved.
- hibernating myocardium
- ischemic heart disease
- stem cell
PubMed: MeSH publication types
- Journal Article