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Human Engineered Heart Tissue as a Versatile Tool in Basic Research and Preclinical Toxicology

Human embryonic stem cell (hESC) progenies hold great promise as surrogates for human primary cells, particularly if the latter are not available as in the case of cardiomyocytes. However, high content experimental platforms are lacking that allow the function of hESC-derived cardiomyocytes to be st...

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Autores principales: Schaaf, Sebastian, Shibamiya, Aya, Mewe, Marco, Eder, Alexandra, Stöhr, Andrea, Hirt, Marc N., Rau, Thomas, Zimmermann, Wolfram-Hubertus, Conradi, Lenard, Eschenhagen, Thomas, Hansen, Arne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197640/
https://www.ncbi.nlm.nih.gov/pubmed/22028871
http://dx.doi.org/10.1371/journal.pone.0026397
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author Schaaf, Sebastian
Shibamiya, Aya
Mewe, Marco
Eder, Alexandra
Stöhr, Andrea
Hirt, Marc N.
Rau, Thomas
Zimmermann, Wolfram-Hubertus
Conradi, Lenard
Eschenhagen, Thomas
Hansen, Arne
author_facet Schaaf, Sebastian
Shibamiya, Aya
Mewe, Marco
Eder, Alexandra
Stöhr, Andrea
Hirt, Marc N.
Rau, Thomas
Zimmermann, Wolfram-Hubertus
Conradi, Lenard
Eschenhagen, Thomas
Hansen, Arne
author_sort Schaaf, Sebastian
collection PubMed
description Human embryonic stem cell (hESC) progenies hold great promise as surrogates for human primary cells, particularly if the latter are not available as in the case of cardiomyocytes. However, high content experimental platforms are lacking that allow the function of hESC-derived cardiomyocytes to be studied under relatively physiological and standardized conditions. Here we describe a simple and robust protocol for the generation of fibrin-based human engineered heart tissue (hEHT) in a 24-well format using an unselected population of differentiated human embryonic stem cells containing 30–40% α-actinin-positive cardiac myocytes. Human EHTs started to show coherent contractions 5–10 days after casting, reached regular (mean 0.5 Hz) and strong (mean 100 µN) contractions for up to 8 weeks. They displayed a dense network of longitudinally oriented, interconnected and cross-striated cardiomyocytes. Spontaneous hEHT contractions were analyzed by automated video-optical recording and showed chronotropic responses to calcium and the β-adrenergic agonist isoprenaline. The proarrhythmic compounds E-4031, quinidine, procainamide, cisapride, and sertindole exerted robust, concentration-dependent and reversible decreases in relaxation velocity and irregular beating at concentrations that recapitulate findings in hERG channel assays. In conclusion this study establishes hEHT as a simple in vitro model for heart research.
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spelling pubmed-31976402011-10-25 Human Engineered Heart Tissue as a Versatile Tool in Basic Research and Preclinical Toxicology Schaaf, Sebastian Shibamiya, Aya Mewe, Marco Eder, Alexandra Stöhr, Andrea Hirt, Marc N. Rau, Thomas Zimmermann, Wolfram-Hubertus Conradi, Lenard Eschenhagen, Thomas Hansen, Arne PLoS One Research Article Human embryonic stem cell (hESC) progenies hold great promise as surrogates for human primary cells, particularly if the latter are not available as in the case of cardiomyocytes. However, high content experimental platforms are lacking that allow the function of hESC-derived cardiomyocytes to be studied under relatively physiological and standardized conditions. Here we describe a simple and robust protocol for the generation of fibrin-based human engineered heart tissue (hEHT) in a 24-well format using an unselected population of differentiated human embryonic stem cells containing 30–40% α-actinin-positive cardiac myocytes. Human EHTs started to show coherent contractions 5–10 days after casting, reached regular (mean 0.5 Hz) and strong (mean 100 µN) contractions for up to 8 weeks. They displayed a dense network of longitudinally oriented, interconnected and cross-striated cardiomyocytes. Spontaneous hEHT contractions were analyzed by automated video-optical recording and showed chronotropic responses to calcium and the β-adrenergic agonist isoprenaline. The proarrhythmic compounds E-4031, quinidine, procainamide, cisapride, and sertindole exerted robust, concentration-dependent and reversible decreases in relaxation velocity and irregular beating at concentrations that recapitulate findings in hERG channel assays. In conclusion this study establishes hEHT as a simple in vitro model for heart research. Public Library of Science 2011-10-20 /pmc/articles/PMC3197640/ /pubmed/22028871 http://dx.doi.org/10.1371/journal.pone.0026397 Text en Schaaf et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Schaaf, Sebastian
Shibamiya, Aya
Mewe, Marco
Eder, Alexandra
Stöhr, Andrea
Hirt, Marc N.
Rau, Thomas
Zimmermann, Wolfram-Hubertus
Conradi, Lenard
Eschenhagen, Thomas
Hansen, Arne
Human Engineered Heart Tissue as a Versatile Tool in Basic Research and Preclinical Toxicology
title Human Engineered Heart Tissue as a Versatile Tool in Basic Research and Preclinical Toxicology
title_full Human Engineered Heart Tissue as a Versatile Tool in Basic Research and Preclinical Toxicology
title_fullStr Human Engineered Heart Tissue as a Versatile Tool in Basic Research and Preclinical Toxicology
title_full_unstemmed Human Engineered Heart Tissue as a Versatile Tool in Basic Research and Preclinical Toxicology
title_short Human Engineered Heart Tissue as a Versatile Tool in Basic Research and Preclinical Toxicology
title_sort human engineered heart tissue as a versatile tool in basic research and preclinical toxicology
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197640/
https://www.ncbi.nlm.nih.gov/pubmed/22028871
http://dx.doi.org/10.1371/journal.pone.0026397
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