Human iPSC-derived cardiomyocytes cultured in 3D engineered heart tissue show physiological upstroke velocity and sodium current density

Abstract Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising tool for drug testing and modelling genetic disorders. Abnormally low upstroke velocity is a current limitation. Here we investigated the use of 3D engineered heart tissue (EHT) as a culture method with gr...

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Autores principales:	Marc D. Lemoine, Ingra Mannhardt, Kaja Breckwoldt, Maksymilian Prondzynski, Frederik Flenner, Bärbel Ulmer, Marc N. Hirt, Christiane Neuber, András Horváth, Benjamin Kloth, Hermann Reichenspurner, Stephan Willems, Arne Hansen, Thomas Eschenhagen, Torsten Christ
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2e69ee578b0a4779a389e8f3a0ff7687
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spelling	oai:doaj.org-article:2e69ee578b0a4779a389e8f3a0ff76872021-12-02T12:32:20ZHuman iPSC-derived cardiomyocytes cultured in 3D engineered heart tissue show physiological upstroke velocity and sodium current density10.1038/s41598-017-05600-w2045-2322https://doaj.org/article/2e69ee578b0a4779a389e8f3a0ff76872017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05600-whttps://doaj.org/toc/2045-2322Abstract Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising tool for drug testing and modelling genetic disorders. Abnormally low upstroke velocity is a current limitation. Here we investigated the use of 3D engineered heart tissue (EHT) as a culture method with greater resemblance to human heart tissue in comparison to standard technique of 2D monolayer (ML) format. INa was measured in ML or EHT using the standard patch-clamp technique. INa density was ~1.8 fold larger in EHT (−18.5 ± 1.9 pA/pF; n = 17) than in ML (−10.3 ± 1.2 pA/pF; n = 23; p < 0.001), approaching densities reported for human CM. Inactivation kinetics, voltage dependency of steady-state inactivation and activation of INa did not differ between EHT and ML and were similar to previously reported values for human CM. Action potential recordings with sharp microelectrodes showed similar upstroke velocities in EHT (219 ± 15 V/s, n = 13) and human left ventricle tissue (LV, 253 ± 7 V/s, n = 25). EHT showed a greater resemblance to LV in CM morphology and subcellular NaV1.5 distribution. INa in hiPSC-CM showed similar biophysical properties as in human CM. The EHT format promotes INa density and action potential upstroke velocity of hiPSC-CM towards adult values, indicating its usefulness as a model for excitability of human cardiac tissue.Marc D. LemoineIngra MannhardtKaja BreckwoldtMaksymilian ProndzynskiFrederik FlennerBärbel UlmerMarc N. HirtChristiane NeuberAndrás HorváthBenjamin KlothHermann ReichenspurnerStephan WillemsArne HansenThomas EschenhagenTorsten ChristNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marc D. Lemoine Ingra Mannhardt Kaja Breckwoldt Maksymilian Prondzynski Frederik Flenner Bärbel Ulmer Marc N. Hirt Christiane Neuber András Horváth Benjamin Kloth Hermann Reichenspurner Stephan Willems Arne Hansen Thomas Eschenhagen Torsten Christ Human iPSC-derived cardiomyocytes cultured in 3D engineered heart tissue show physiological upstroke velocity and sodium current density
description	Abstract Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising tool for drug testing and modelling genetic disorders. Abnormally low upstroke velocity is a current limitation. Here we investigated the use of 3D engineered heart tissue (EHT) as a culture method with greater resemblance to human heart tissue in comparison to standard technique of 2D monolayer (ML) format. INa was measured in ML or EHT using the standard patch-clamp technique. INa density was ~1.8 fold larger in EHT (−18.5 ± 1.9 pA/pF; n = 17) than in ML (−10.3 ± 1.2 pA/pF; n = 23; p < 0.001), approaching densities reported for human CM. Inactivation kinetics, voltage dependency of steady-state inactivation and activation of INa did not differ between EHT and ML and were similar to previously reported values for human CM. Action potential recordings with sharp microelectrodes showed similar upstroke velocities in EHT (219 ± 15 V/s, n = 13) and human left ventricle tissue (LV, 253 ± 7 V/s, n = 25). EHT showed a greater resemblance to LV in CM morphology and subcellular NaV1.5 distribution. INa in hiPSC-CM showed similar biophysical properties as in human CM. The EHT format promotes INa density and action potential upstroke velocity of hiPSC-CM towards adult values, indicating its usefulness as a model for excitability of human cardiac tissue.
format	article
author	Marc D. Lemoine Ingra Mannhardt Kaja Breckwoldt Maksymilian Prondzynski Frederik Flenner Bärbel Ulmer Marc N. Hirt Christiane Neuber András Horváth Benjamin Kloth Hermann Reichenspurner Stephan Willems Arne Hansen Thomas Eschenhagen Torsten Christ
author_facet	Marc D. Lemoine Ingra Mannhardt Kaja Breckwoldt Maksymilian Prondzynski Frederik Flenner Bärbel Ulmer Marc N. Hirt Christiane Neuber András Horváth Benjamin Kloth Hermann Reichenspurner Stephan Willems Arne Hansen Thomas Eschenhagen Torsten Christ
author_sort	Marc D. Lemoine
title	Human iPSC-derived cardiomyocytes cultured in 3D engineered heart tissue show physiological upstroke velocity and sodium current density
title_short	Human iPSC-derived cardiomyocytes cultured in 3D engineered heart tissue show physiological upstroke velocity and sodium current density
title_full	Human iPSC-derived cardiomyocytes cultured in 3D engineered heart tissue show physiological upstroke velocity and sodium current density
title_fullStr	Human iPSC-derived cardiomyocytes cultured in 3D engineered heart tissue show physiological upstroke velocity and sodium current density
title_full_unstemmed	Human iPSC-derived cardiomyocytes cultured in 3D engineered heart tissue show physiological upstroke velocity and sodium current density
title_sort	human ipsc-derived cardiomyocytes cultured in 3d engineered heart tissue show physiological upstroke velocity and sodium current density
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2e69ee578b0a4779a389e8f3a0ff7687
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Human iPSC-derived cardiomyocytes cultured in 3D engineered heart tissue show physiological upstroke velocity and sodium current density

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