The electrocardiogram of human embryonic stem cell-derived cardiomyocytes.
Microelectrode arrays enable to map extracellular field potentials of excitable organs (eg, cardiac tissue) in an electrocardiogram-like manner: They allow to detect (a) rhythmicity, (b) the origin and route of excitation, (c) repolarization, and (d) conduction in heart tissue in short- and long-term experimental approaches. Using it as a screening tool for potential side effects of drugs, we here provide evidence for d-sotalol-induced delayed repolarization in human embryonic stem (hES) cell-derived cardiomyocytes. Thus, the combination of the microelectrode array system with cardiac clusters derived from hES cells heralds a paradigm shift toward improved pharmaceutical drug safety. However, the mixture of various cell types in hES cell cardiac clusters (eg, atrial, immature and mature ventricular cardiomyocytes) indicates the strong need for improved selectivity of cardiac differentiation protocols using hES cells.
Reppel
Michael
M
Institute of Neurophysiology, University of Cologne, D-50931 Cologne, Germany. akp72@uni-koeln.de
Pillekamp
Frank
F
Brockmeier
Konrad
K
Matzkies
Matthias
M
Bekcioglu
Aret
A
Lipke
Teresa
T
Nguemo
Filomain
F
Bonnemeier
Hendrik
H
Hescheler
Juergen
J
D000200:Action Potentials / Q000187:drug effects; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D004622:Embryo, Mammalian / Q000166:cytology* / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects / Q000196:embryology; D006801:Humans; D008839:Microelectrodes; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D013015:Sotalol / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D013015:Sotalol