Recovery of hibernating myocardium using stem cell patch with coronary bypass surgery

Laura L. Hocum Stone; Cory Swingen; Christin Wright; Steven S. Qi; Matt Rassette; Edward O. McFalls; Rosemary F. Kelly

doi:10.1016/j.jtcvs.2019.12.073

Recovery of hibernating myocardium using stem cell patch with coronary bypass surgery

Laura L. Hocum Stone, Cory Swingen, Christin Wright, Steven S. Qi, Matt Rassette, Edward O. McFalls, Rosemary F. Kelly

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English (US)
Pages (from-to)	e3-e16
Journal	Journal of Thoracic and Cardiovascular Surgery
Volume	162
Issue number	1
Early online date	Jan 11 2020
DOIs	https://doi.org/10.1016/j.jtcvs.2019.12.073
State	Published - Jul 2021

Bibliographical note

Funding 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.

Funding 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.

Publisher Copyright:
© 2020 The American Association for Thoracic Surgery

Keywords

MSC
hibernating myocardium
ischemic heart disease
mitochondria
stem cell
Myocardial Stunning/physiopathology
Myocardial Ischemia
Animals
Swine
Coronary Artery Bypass
Female
Mesenchymal Stem Cell Transplantation
Disease Models, Animal

PubMed: MeSH publication types

Research Support, U.S. Gov't, Non-P.H.S.
Journal Article

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10.1016/j.jtcvs.2019.12.073

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title = "Recovery of hibernating myocardium using stem cell patch with coronary bypass surgery",

abstract = "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.",

keywords = "MSC, hibernating myocardium, ischemic heart disease, mitochondria, stem cell, Myocardial Stunning/physiopathology, Myocardial Ischemia, Animals, Swine, Coronary Artery Bypass, Female, Mesenchymal Stem Cell Transplantation, Disease Models, Animal",

author = "{Hocum Stone}, {Laura L.} and Cory Swingen and Christin Wright and Qi, {Steven S.} and Matt Rassette and McFalls, {Edward O.} and Kelly, {Rosemary F.}",

note = "Funding 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. Funding 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. Publisher Copyright: {\textcopyright} 2020 The American Association for Thoracic Surgery",

year = "2021",

month = jul,

doi = "10.1016/j.jtcvs.2019.12.073",

language = "English (US)",

volume = "162",

pages = "e3--e16",

journal = "Journal of Thoracic and Cardiovascular Surgery",

issn = "0022-5223",

publisher = "Mosby Inc.",

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TY - JOUR

T1 - Recovery of hibernating myocardium using stem cell patch with coronary bypass surgery

AU - Hocum Stone, Laura L.

AU - Swingen, Cory

AU - Wright, Christin

AU - Qi, Steven S.

AU - Rassette, Matt

AU - McFalls, Edward O.

AU - Kelly, Rosemary F.

N1 - Funding 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. Funding 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. Publisher Copyright: © 2020 The American Association for Thoracic Surgery

PY - 2021/7

Y1 - 2021/7

N2 - 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.

AB - 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.

KW - MSC

KW - hibernating myocardium

KW - ischemic heart disease

KW - mitochondria

KW - stem cell

KW - Myocardial Stunning/physiopathology

KW - Myocardial Ischemia

KW - Animals

KW - Swine

KW - Coronary Artery Bypass

KW - Female

KW - Mesenchymal Stem Cell Transplantation

KW - Disease Models, Animal

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Recovery of hibernating myocardium using stem cell patch with coronary bypass surgery

Abstract

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Keywords

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