High-performance beating pattern function of human induced pluripotent stem cell-derived cardiomyocyte-based biosensors for hERG inhibition recognition

Biosens Bioelectron. 2015 May 15:67:146-53. doi: 10.1016/j.bios.2014.07.080. Epub 2014 Aug 12.

Abstract

High-throughput and high clinical relevance methods are demanded to predict the drug-induced cardiotoxicity in pharmaceutical and biotechnology industries to effectively decrease late-stage drug attrition. In this study, human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were integrated into an interdigital impedance sensor array to fabricate a high performance iPSC-CM-based biosensor array with high-throughput and high-consistency beating pattern. Typical withdrawal approved drugs (astemizole, sertindole, cisapride, and droperidol) with hERG inhibition and positive control E-4031 were employed to determine the beating pattern function. From the results, it can be concluded that this iPSC-CM-based biosensor array can specifically differentiate the hERG inhibitors from the non-hERG inhibition compounds through beating pattern function.

Keywords: Beating pattern function; Drug cardiotoxicity assessment; Human iPSC-CM-based biosensor array; Impedance detection technology; hERG inhibitor recognition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Assay / instrumentation
  • Biosensing Techniques / instrumentation*
  • Cell Differentiation
  • Cells, Cultured
  • Conductometry / instrumentation*
  • ERG1 Potassium Channel
  • Equipment Design
  • Equipment Failure Analysis
  • Ether-A-Go-Go Potassium Channels / antagonists & inhibitors*
  • Heart Rate / drug effects
  • Heart Rate / physiology*
  • Humans
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / physiology*
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / drug effects
  • Pluripotent Stem Cells / physiology
  • Potassium Channel Blockers / pharmacology*
  • Reproducibility of Results
  • Sensitivity and Specificity

Substances

  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • KCNH2 protein, human
  • Potassium Channel Blockers