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Human Pluripotent Stem Cell-Derived Cardiomyocytes: Response to TTX and Lidocain Reveals Strong Cell to Cell Variability

Stem cell derived cardiomyocytes generated either from human embryonic stem cells (hESC-CMs) or human induced pluripotent stem cells (hiPSC-CMs) hold great promise for the investigation of early developmental processes in human cardiomyogenesis and future cell replacement strategies. We have analyze...

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Autores principales: Sheng, Xiaowu, Reppel, Michael, Nguemo, Filomain, Mohammad, Farooq Ibrahem, Kuzmenkin, Alexey, Hescheler, Jürgen, Pfannkuche, Kurt
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459939/
https://www.ncbi.nlm.nih.gov/pubmed/23029342
http://dx.doi.org/10.1371/journal.pone.0045963
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author Sheng, Xiaowu
Reppel, Michael
Nguemo, Filomain
Mohammad, Farooq Ibrahem
Kuzmenkin, Alexey
Hescheler, Jürgen
Pfannkuche, Kurt
author_facet Sheng, Xiaowu
Reppel, Michael
Nguemo, Filomain
Mohammad, Farooq Ibrahem
Kuzmenkin, Alexey
Hescheler, Jürgen
Pfannkuche, Kurt
author_sort Sheng, Xiaowu
collection PubMed
description Stem cell derived cardiomyocytes generated either from human embryonic stem cells (hESC-CMs) or human induced pluripotent stem cells (hiPSC-CMs) hold great promise for the investigation of early developmental processes in human cardiomyogenesis and future cell replacement strategies. We have analyzed electrophysiological properties of hESC-CMs (HES2) and hiPSC-CMs, derived from reprogrammed adult foreskin fibroblasts that have previously been found to be highly similar in terms of gene expression. In contrast to the similarity found in the expression profile we found substantial differences in action potentials (APs) and sodium currents at late stage (day 60) of in vitro differentiation with higher sodium currents in hiPSC-CMs. Sensitivity to lidocain was considerably reduced in hESC-CMs as compared to hiPSC-CMs, and the effect could not be explained by differences in beating frequency. In contrast, sensitivity to tetrodotoxin (TTX) was higher in hESC-CMs suggesting different contributions of TTX-sensitive and TTX-resistant sodium channels to AP generation. These data point to physiological differences that are not necessarily detected by genomics. We conclude that novel pharmacological screening-assays using hiPSC-CMs need to be applied with some caution.
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spelling pubmed-34599392012-10-01 Human Pluripotent Stem Cell-Derived Cardiomyocytes: Response to TTX and Lidocain Reveals Strong Cell to Cell Variability Sheng, Xiaowu Reppel, Michael Nguemo, Filomain Mohammad, Farooq Ibrahem Kuzmenkin, Alexey Hescheler, Jürgen Pfannkuche, Kurt PLoS One Research Article Stem cell derived cardiomyocytes generated either from human embryonic stem cells (hESC-CMs) or human induced pluripotent stem cells (hiPSC-CMs) hold great promise for the investigation of early developmental processes in human cardiomyogenesis and future cell replacement strategies. We have analyzed electrophysiological properties of hESC-CMs (HES2) and hiPSC-CMs, derived from reprogrammed adult foreskin fibroblasts that have previously been found to be highly similar in terms of gene expression. In contrast to the similarity found in the expression profile we found substantial differences in action potentials (APs) and sodium currents at late stage (day 60) of in vitro differentiation with higher sodium currents in hiPSC-CMs. Sensitivity to lidocain was considerably reduced in hESC-CMs as compared to hiPSC-CMs, and the effect could not be explained by differences in beating frequency. In contrast, sensitivity to tetrodotoxin (TTX) was higher in hESC-CMs suggesting different contributions of TTX-sensitive and TTX-resistant sodium channels to AP generation. These data point to physiological differences that are not necessarily detected by genomics. We conclude that novel pharmacological screening-assays using hiPSC-CMs need to be applied with some caution. Public Library of Science 2012-09-27 /pmc/articles/PMC3459939/ /pubmed/23029342 http://dx.doi.org/10.1371/journal.pone.0045963 Text en © 2012 Sheng 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
Sheng, Xiaowu
Reppel, Michael
Nguemo, Filomain
Mohammad, Farooq Ibrahem
Kuzmenkin, Alexey
Hescheler, Jürgen
Pfannkuche, Kurt
Human Pluripotent Stem Cell-Derived Cardiomyocytes: Response to TTX and Lidocain Reveals Strong Cell to Cell Variability
title Human Pluripotent Stem Cell-Derived Cardiomyocytes: Response to TTX and Lidocain Reveals Strong Cell to Cell Variability
title_full Human Pluripotent Stem Cell-Derived Cardiomyocytes: Response to TTX and Lidocain Reveals Strong Cell to Cell Variability
title_fullStr Human Pluripotent Stem Cell-Derived Cardiomyocytes: Response to TTX and Lidocain Reveals Strong Cell to Cell Variability
title_full_unstemmed Human Pluripotent Stem Cell-Derived Cardiomyocytes: Response to TTX and Lidocain Reveals Strong Cell to Cell Variability
title_short Human Pluripotent Stem Cell-Derived Cardiomyocytes: Response to TTX and Lidocain Reveals Strong Cell to Cell Variability
title_sort human pluripotent stem cell-derived cardiomyocytes: response to ttx and lidocain reveals strong cell to cell variability
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459939/
https://www.ncbi.nlm.nih.gov/pubmed/23029342
http://dx.doi.org/10.1371/journal.pone.0045963
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