In vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes.
The lethal ventricular arrhythmia Torsade de pointes (TdP) is the most common reason for the withdrawal or restricted use of many cardiovascular and non-cardiovascular drugs. The lack of an in vitro model to detect pro-arrhythmic effects on human heart cells hinders the development of new drugs. We hypothesized that recently established human induced pluripotent stem (hiPS) cells could be used in an in vitro drug screening model. In this study, hiPS cells were driven to differentiate into functional cardiomyocytes, which expressed cardiac markers including Nkx2.5, GATA4, and atrial natriuretic peptide. The hiPS-derived cardiomyocytes (hiPS-CMs) were analyzed using a multi electrode assay. The application of ion channel inhibitors resulted in dose-dependent changes to the field potential waveform, and these changes were identical to those induced in the native cardiomyocytes. This study shows that hiPS-CMs represent a promising in vitro model for cardiac electrophysiologic studies and drug screening.
Tanaka
Tomofumi
T
Department of Regenerative Medicine and Advanced Cardiac Therapeutics, School of Medicine, Keio University, Tokyo, Japan.
Tohyama
Shugo
S
Murata
Mitsushige
M
Nomura
Fumimasa
F
Kaneko
Tomoyuki
T
Chen
Hao
H
Hattori
Fumiyuki
F
Egashira
Toru
T
Seki
Tomohisa
T
Ohno
Yohei
Y
Koshimizu
Uichi
U
Yuasa
Shinsuke
S
Ogawa
Satoshi
S
Yamanaka
Shinya
S
Yasuda
Kenji
K
Fukuda
Keiichi
K
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000379:methods; D050991:GATA4 Transcription Factor / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006321:Heart / Q000502:physiology; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000235:genetics; D007545:Isoproterenol / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics
D000318:Adrenergic beta-Agonists; D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D005819:Genetic Markers; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D007473:Ion Channels; C095552:NKX2-5 protein, human; D014157:Transcription Factors; D009320:Atrial Natriuretic Factor; D007545:Isoproterenol