Universität zu Köln

Sheng, Xiaowu, Reppel, Michael, Nguemo, Filomain, Mohammad, Farooq Ibrahem, Kuzmenkin, Alexey, Hescheler, Juergen and Pfannkuche, Kurt (2012). Human Pluripotent Stem Cell-Derived Cardiomyocytes: Response to TTX and Lidocain Reveals Strong Cell to Cell Variability. PLoS One, 7 (9). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Sheng, Xiaowu UNSPECIFIED UNSPECIFIED UNSPECIFIED Reppel, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Nguemo, Filomain UNSPECIFIED UNSPECIFIED UNSPECIFIED Mohammad, Farooq Ibrahem UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuzmenkin, Alexey UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfannkuche, Kurt UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-482763
DOI:	10.1371/journal.pone.0045963
Journal or Publication Title:	PLoS One
Volume:	7
Number:	9
Date:	2012
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CARDIAC MYOCYTES; HUMAN FIBROBLASTS; SODIUM CURRENT; NA+ CURRENT; GENERATION; MOUSE; INDUCTION; DIFFERENTIATION; TRANSPLANTATION; INTEGRATION Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48276