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Functional Properties of Engineered Heart Slices Incorporating Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for cardiac studies, but their structural and functional immaturity precludes their use as faithful models of adult myocardium. Here we describe engineered heart slices (EHS), preparations of decellularized por...

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Detalles Bibliográficos
Autores principales: Blazeski, Adriana, Lowenthal, Justin, Zhu, Renjun, Ewoldt, Jourdan, Boheler, Kenneth R., Tung, Leslie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524004/
https://www.ncbi.nlm.nih.gov/pubmed/31056480
http://dx.doi.org/10.1016/j.stemcr.2019.04.002
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author Blazeski, Adriana
Lowenthal, Justin
Zhu, Renjun
Ewoldt, Jourdan
Boheler, Kenneth R.
Tung, Leslie
author_facet Blazeski, Adriana
Lowenthal, Justin
Zhu, Renjun
Ewoldt, Jourdan
Boheler, Kenneth R.
Tung, Leslie
author_sort Blazeski, Adriana
collection PubMed
description Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for cardiac studies, but their structural and functional immaturity precludes their use as faithful models of adult myocardium. Here we describe engineered heart slices (EHS), preparations of decellularized porcine myocardium repopulated with hiPSC-CMs that exhibit structural and functional improvements over standard culture. EHS exhibited multicellular, aligned bundles of elongated CMs with organized sarcomeres, positive inotropic responses to isoproterenol, anisotropic conduction of action potentials, and electrophysiological functionality for more than 200 days. We developed a new drug assay, GRIDS, that serves as a “fingerprint” of cardiac drug sensitivity for a range of pacing rates and drug concentrations. GRIDS maps characterized differences in drug sensitivity between EHS and monolayers more clearly than changes in action potential durations or conduction velocities. EHS represent a tissue-like model for long-term culture, structural, and functional improvement, and higher fidelity drug response of hiPSC-CMs.
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spelling pubmed-65240042019-05-24 Functional Properties of Engineered Heart Slices Incorporating Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Blazeski, Adriana Lowenthal, Justin Zhu, Renjun Ewoldt, Jourdan Boheler, Kenneth R. Tung, Leslie Stem Cell Reports Article Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for cardiac studies, but their structural and functional immaturity precludes their use as faithful models of adult myocardium. Here we describe engineered heart slices (EHS), preparations of decellularized porcine myocardium repopulated with hiPSC-CMs that exhibit structural and functional improvements over standard culture. EHS exhibited multicellular, aligned bundles of elongated CMs with organized sarcomeres, positive inotropic responses to isoproterenol, anisotropic conduction of action potentials, and electrophysiological functionality for more than 200 days. We developed a new drug assay, GRIDS, that serves as a “fingerprint” of cardiac drug sensitivity for a range of pacing rates and drug concentrations. GRIDS maps characterized differences in drug sensitivity between EHS and monolayers more clearly than changes in action potential durations or conduction velocities. EHS represent a tissue-like model for long-term culture, structural, and functional improvement, and higher fidelity drug response of hiPSC-CMs. Elsevier 2019-05-02 /pmc/articles/PMC6524004/ /pubmed/31056480 http://dx.doi.org/10.1016/j.stemcr.2019.04.002 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Blazeski, Adriana
Lowenthal, Justin
Zhu, Renjun
Ewoldt, Jourdan
Boheler, Kenneth R.
Tung, Leslie
Functional Properties of Engineered Heart Slices Incorporating Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
title Functional Properties of Engineered Heart Slices Incorporating Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
title_full Functional Properties of Engineered Heart Slices Incorporating Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
title_fullStr Functional Properties of Engineered Heart Slices Incorporating Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
title_full_unstemmed Functional Properties of Engineered Heart Slices Incorporating Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
title_short Functional Properties of Engineered Heart Slices Incorporating Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
title_sort functional properties of engineered heart slices incorporating human induced pluripotent stem cell-derived cardiomyocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524004/
https://www.ncbi.nlm.nih.gov/pubmed/31056480
http://dx.doi.org/10.1016/j.stemcr.2019.04.002
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