Fundamental Toxicological Sciences

Paper Details

Fundamental Toxicological Sciences
Vol. 3 No. 2 February 26, 2016 p.47-53
Differing responses of human stem cell-derived cardiomyocytes to arrhythmogenic drugs, determined using impedance measurements
  • Motoki Takagi (Medical-industrial Translational Research Center, Fukushima Medical University /
Arisa Higa , Hirotaka Hoshi , Motoki Takagi
Medical-industrial Translational Research Center, Fukushima Medical University
Keywords: Arrhythmia, Cardiotoxicity, hiPS cell-derived cardiomyocytes, hES cell-derived cardiomyocytes, Impedance measurement, xCELLigence

In recent years, human induced pluripotent stem cell-derived cardiomyocytes (hiPSCMs) and human embryonic stem cell-derived cardiomyocytes (hES-CMs) have been widely used to develop cardiotoxicity assessment systems. To accurately evaluate the arrhythmogenic potential of drugs, we tested three types of hiPS-CMs (iCell Cardiomyocytes, Cellartis hiPS-CM, and Cor.4U) and a type of hES-CMs (Cellartis Pure hES-CM) using impedance technology. All CMs were cultured as confluent monolayers and their beating activity was analyzed with an impedance-based real-time monitoring instrument, the xCELLigence RTCA Cardio System. Measurement of impedance provided information about the CM beating rate and impedance amplitude between negative and positive peaks. Although all CMs except iCell CMs showed similar beating rates, their amplitudes were different. In addition, the patterns of contraction and relaxation were notably different between iCell CMs and the other CMs. The hiPSCMs and hES-CMs were treated with two arrhythmogenic drugs, sotalol and moxifloxacin, for 24 hr; the results showed that the drugs induced arrhythmic beating patterns on all CMs, although the response was varied. Thus, a more suitable type of CM remains to be found for optimal evaluation of the arrhythmogenic potential of drugs.