Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Encapsulating Bioactive Hydrogels Improve Rat Heart Function Post Myocardial Infarction

Summary: Tissue engineering offers an exciting possibility for cardiac repair post myocardial infarction. We assessed the effects of combined polyethylene glycol hydrogel (PEG), human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM), and erythropoietin (EPO) therapy in a rat model of my...

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Main Authors: Andre Chow, Daniel J. Stuckey, Emaddin Kidher, Mark Rocco, Richard J. Jabbour, Catherine A. Mansfield, Ara Darzi, Sian E. Harding, Molly M. Stevens, Thanos Athanasiou
Format: Article
Language:English
Published: Elsevier 2017-11-01
Series:Stem Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671117303867
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spelling doaj-8f9988c0851646a685eb072b0053923a2020-11-25T01:09:10ZengElsevierStem Cell Reports2213-67112017-11-019514151422Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Encapsulating Bioactive Hydrogels Improve Rat Heart Function Post Myocardial InfarctionAndre Chow0Daniel J. Stuckey1Emaddin Kidher2Mark Rocco3Richard J. Jabbour4Catherine A. Mansfield5Ara Darzi6Sian E. Harding7Molly M. Stevens8Thanos Athanasiou9Department of Surgery and Cancer, Imperial College London, St Mary's Hospital, London W2 1NY, UKCentre for Advanced Biomedical Imaging, University College London, London WC1E 6DD, UK; National Heart & Lung Institute, Imperial College London, Hammersmith Campus, London W12 0NN, UKDepartment of Surgery and Cancer, Imperial College London, St Mary's Hospital, London W2 1NY, UKDepartment of Materials, Faculty of Engineering, Imperial College London, South Kensington, London SW7 2AZ, UK; Department of Bioengineering, Imperial College London, London SW7 2AZ, UK; Institute for Biomedical Engineering, Imperial College London, London SW7 2AZ, UKNational Heart & Lung Institute, Imperial College London, Hammersmith Campus, London W12 0NN, UKNational Heart & Lung Institute, Imperial College London, Hammersmith Campus, London W12 0NN, UKDepartment of Surgery and Cancer, Imperial College London, St Mary's Hospital, London W2 1NY, UKNational Heart & Lung Institute, Imperial College London, Hammersmith Campus, London W12 0NN, UK; Corresponding authorDepartment of Materials, Faculty of Engineering, Imperial College London, South Kensington, London SW7 2AZ, UK; Department of Bioengineering, Imperial College London, London SW7 2AZ, UK; Institute for Biomedical Engineering, Imperial College London, London SW7 2AZ, UK; Corresponding authorDepartment of Surgery and Cancer, Imperial College London, St Mary's Hospital, London W2 1NY, UKSummary: Tissue engineering offers an exciting possibility for cardiac repair post myocardial infarction. We assessed the effects of combined polyethylene glycol hydrogel (PEG), human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM), and erythropoietin (EPO) therapy in a rat model of myocardial infarction. PEG with/out iPSC-CMs and EPO; iPSC-CMs in saline; or saline alone was injected into infarcted hearts shortly after infarction. Injection of almost any combination of the therapeutics limited acute elevations in chamber volumes. After 10 weeks, attenuation of ventricular remodeling was identified in all groups that received PEG injections, while ejection fractions were significantly increased in the gel-EPO, cell, and gel-cell-EPO groups. In all treatment groups, infarct thickness was increased and regions of muscle were identified within the scar. However, no grafted cells were detected. Hence, iPSC-CM-encapsulating bioactive hydrogel therapy can improve cardiac function post myocardial infarction and increase infarct thickness and muscle content despite a lack of sustained donor-cell engraftment. : Human iPSC-derived cardiomyocyte-encapsulating bioactive hydrogel therapy can improve cardiac function post myocardial infarction and increase infarct thickness and muscle content despite a lack of sustained donor-cell engraftment. This novel combination of injectable hydrogels, iPSCs, and the cardioprotective molecule EPO provides a highly translational strategy with excellent potential for prevention of cardiac failure. Keywords: myocardial infarction, rat, myocardial tissue engineering, hydrogel, induced pluripotent stem cell-derived cardiomyocytes, iPSC-CMs, MRI, erythropoietinhttp://www.sciencedirect.com/science/article/pii/S2213671117303867
collection DOAJ
language English
format Article
sources DOAJ
author Andre Chow
Daniel J. Stuckey
Emaddin Kidher
Mark Rocco
Richard J. Jabbour
Catherine A. Mansfield
Ara Darzi
Sian E. Harding
Molly M. Stevens
Thanos Athanasiou
spellingShingle Andre Chow
Daniel J. Stuckey
Emaddin Kidher
Mark Rocco
Richard J. Jabbour
Catherine A. Mansfield
Ara Darzi
Sian E. Harding
Molly M. Stevens
Thanos Athanasiou
Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Encapsulating Bioactive Hydrogels Improve Rat Heart Function Post Myocardial Infarction
Stem Cell Reports
author_facet Andre Chow
Daniel J. Stuckey
Emaddin Kidher
Mark Rocco
Richard J. Jabbour
Catherine A. Mansfield
Ara Darzi
Sian E. Harding
Molly M. Stevens
Thanos Athanasiou
author_sort Andre Chow
title Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Encapsulating Bioactive Hydrogels Improve Rat Heart Function Post Myocardial Infarction
title_short Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Encapsulating Bioactive Hydrogels Improve Rat Heart Function Post Myocardial Infarction
title_full Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Encapsulating Bioactive Hydrogels Improve Rat Heart Function Post Myocardial Infarction
title_fullStr Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Encapsulating Bioactive Hydrogels Improve Rat Heart Function Post Myocardial Infarction
title_full_unstemmed Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Encapsulating Bioactive Hydrogels Improve Rat Heart Function Post Myocardial Infarction
title_sort human induced pluripotent stem cell-derived cardiomyocyte encapsulating bioactive hydrogels improve rat heart function post myocardial infarction
publisher Elsevier
series Stem Cell Reports
issn 2213-6711
publishDate 2017-11-01
description Summary: Tissue engineering offers an exciting possibility for cardiac repair post myocardial infarction. We assessed the effects of combined polyethylene glycol hydrogel (PEG), human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM), and erythropoietin (EPO) therapy in a rat model of myocardial infarction. PEG with/out iPSC-CMs and EPO; iPSC-CMs in saline; or saline alone was injected into infarcted hearts shortly after infarction. Injection of almost any combination of the therapeutics limited acute elevations in chamber volumes. After 10 weeks, attenuation of ventricular remodeling was identified in all groups that received PEG injections, while ejection fractions were significantly increased in the gel-EPO, cell, and gel-cell-EPO groups. In all treatment groups, infarct thickness was increased and regions of muscle were identified within the scar. However, no grafted cells were detected. Hence, iPSC-CM-encapsulating bioactive hydrogel therapy can improve cardiac function post myocardial infarction and increase infarct thickness and muscle content despite a lack of sustained donor-cell engraftment. : Human iPSC-derived cardiomyocyte-encapsulating bioactive hydrogel therapy can improve cardiac function post myocardial infarction and increase infarct thickness and muscle content despite a lack of sustained donor-cell engraftment. This novel combination of injectable hydrogels, iPSCs, and the cardioprotective molecule EPO provides a highly translational strategy with excellent potential for prevention of cardiac failure. Keywords: myocardial infarction, rat, myocardial tissue engineering, hydrogel, induced pluripotent stem cell-derived cardiomyocytes, iPSC-CMs, MRI, erythropoietin
url http://www.sciencedirect.com/science/article/pii/S2213671117303867
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