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Cardiomyocyte clusters derived from human embryonic stem cells share similarities with human heart tissue.

Journal article
Authors Julia Asp
Daniella Steel
Marianne Jonsson
Caroline Améen
Kerstin Dahlenborg
Anders Jeppsson
Anders Lindahl
Peter Sartipy
Published in Journal of molecular cell biology
Volume 2
Issue 5
Pages 276-83
ISSN 1759-4685
Publication year 2010
Published at Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 276-83
Language en
Links dx.doi.org/10.1093/jmcb/mjq022
Subject categories Cell biology

Abstract

Cardiotoxicity testing is a key activity in the pharmaceutical industry in order to detect detrimental effects of new drugs. A reliable human in vitro model would both be beneficial in selection of lead compounds and be important for reducing animal experimentation. However, the human heart is a complex organ composed of many distinct types of cardiomyocytes, but cardiomyocyte clusters (CMCs) derived from human embryonic stem cells could be an option for a cellular model. Data on functional properties of CMCs demonstrate similarities to their in vivo analogues in human. However, development of an in vitro model requires a more thorough comparison of CMCs to human heart tissue. Therefore, we directly compared individually isolated CMCs to human fetal, neonatal, adult atrial and ventricular heart tissues. Real-time qPCR analysis of mRNA levels and protein staining of ion channels and cardiac markers showed in general a similar expression pattern in CMCs and human heart. Moreover, a significant decrease in beat frequency was noted after addition of Zatebradine, a blocker to I(f) involved in regulation of spontaneous contraction in CMCs. The results underscore the similarities of CMCs to human cardiac tissue, and further support establishment of novel cardiotoxicity assays based on the CMCs in drug discovery.

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