Combination of functional cardiomyocytes derived from human stem cells and a highly-efficient microelectrode array system: an ideal hybrid model assay for drug development.
Human pluripotential stem cells including both embryonic stem cells (hESC) and induced pluripotent stem cells (hiPSC) possess self-renewing potency and pluripotentency and can differentiate into virtually any somatic cell type. These features are a distinct advantage for the generation of specific types of human tissue cells in vitro for continuous use in drug development. Recently, an assay system for drug-induced QT interval prolongation using hESC/hiPSC-derived cardiomyocytes and microelectrode arrays (MEA) has been developed. Drug-induced QT interval prolongation (DIQTIP) can lead to sudden cardiac death and is a major safety concern for the drug industry. Regulatory authorities such as the US FDA and the European Medicines Agency require in-vitro testing of all drug candidates to identify potential risk of DIQTIP prior to clinical trials. To reduce the risk of DIQTIP, a routine assay system for in vitro electrophysiological properties using cell-based assays is effective and necessary in early phase of drug discovery. This review discusses developments over the last couple of years for a qualified drug testing method and provides some examples of how hESC/hiPSC-derived cardiomyocytes are beginning to find a practical use for drug discovery and development.
Asai
Yasuyuki
Y
ReproCELL Inc., KDX Shin-yokohama 381 Bldg, Kohoku-ku Yokoham, Kanagawa, Japan. y-asai@reprocell.com
Tada
Masako
M
Otsuji
Tomomi G
TG
Nakatsuji
Norio
N
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D002454:Cell Differentiation; D015195:Drug Design; D004594:Electrophysiology / Q000295:instrumentation / Q000379:methods*; D006329:Heart Conduction System / Q000502:physiology*; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008839:Microelectrodes; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*
D007473:Ion Channels