Circulation Research. 2002;91:659-661
Published online before print September 26, 2002, doi: 10.1161/01.RES.0000039084.30342.9B
Published online before print September 26, 2002, doi: 10.1161/01.RES.0000039084.30342.9B
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© 2002 American Heart Association, Inc.
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High-Resolution Electrophysiological Assessment of Human Embryonic Stem Cell-Derived Cardiomyocytes
A Novel In Vitro Model for the Study of Conduction
From the Cardiovascular Research Laboratory (I.K., A.G., A.S., L.G.), the Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Rappaport Family Institute for Research in the Medical Sciences, and the Department of Obstetrics and Gynecology (J.I.-E.), Rambam Medical Center, Haifa, Israel.
Correspondence to Lior Gepstein, MD, PhD, The Bruce Rappaport Faculty of Medicine, Technion, 2 Efron St, POB 9649, Haifa, 31096, Israel. E-mail mdlior{at}tx.technion.ac.il
Abstract
The goal of the present report was to establish a new in vitro model for the study of impulse propagation in human cardiac tissue. By using the human embryonic stem cell differentiating system, spontaneously contracting areas were generated in three-dimensional differentiating cell aggregates (embryoid bodies). Morphological analysis revealed an isotropic tissue of early-stage cardiac phenotype. Gap junctions, assessed by immunostaining of connexin43 and connexin45, were distributed along the cell borders. High-resolution activation maps demonstrated the presence of a functional syncytium with stable focal activation and conduction properties. Conduction was significantly slower in narrow bands of contracting tissue compared with broad cardiomyocyte regions. Establishment of this unique in vitro human model may be used for the assessment of long-term structure-function relationships, for pharmacological studies, for tissue engineering, and may permit the study of genetically modified cardiomyocytes.
Key Words: conduction • gap junctions • embryonic stem cells • mapping
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