title: Induced pluripotent stem cells as cardiac arrhythmic in vitro models and the impact for drug discovery.
abstract: BACKGROUND
  The development of new antiarrhythmic agents is challenging and is hampered by high attrition rate of novel drug candidates. One of the reasons for this is limited predictability of existing preclinical models for drug assessment. Cardiomyocytes (CMs) derived from disease-specific induced pluripotent stem cells (iPSC) represent a novel in vitro cellular model of cardiac arrhythmias with an unprecedented potential for generating new mechanistic insight into disease pathophysiology and improving the process of drug development.
  
  
  METHODS
  This review outlines recent studies demonstrating the suitability and limitations of iPSC-derived CMs (iPS-CMs) for in vitro modeling inherited arrhythmias and drug testing. The authors focus on channelopathies and outline the properties of iPS-CMs, highlighting their utility and limitations for investigating the mechanism of cardiac arrhythmias and drug discovery.
  
  
  CONCLUSIONS
  The iPS-CMs represent a valuable addition to the already existing armamentarium of cardiac arrhythmic models. However, the superiority of iPS-CMs over other arrhythmia models has not yet been rigorously established and the limitations of the model must be overcome before its full potential for antiarrhythmic drug discovery can be realized. Nevertheless, iPS cell-based platforms hold a great potential for increasing our knowledge about cellular arrhythmia mechanisms and improving the drug discovery process.
authors.affiliation: University of Cologne, Institute for Neurophysiology, Center for Physiology and Pathophysiology, Medical Center , Robert Koch Str. 39, 50931 Cologne , Germany +49 221 478 86686 ; +49 221 478-3834 ; tomo.saric@uni-koeln.de.
authors.forename: Tomo
authors.initials: T
authors.lastname: Sarić
authors.forename: Marcel
authors.initials: M
authors.lastname: Halbach
authors.forename: Markus
authors.initials: M
authors.lastname: Khalil
authors.forename: Fikret
authors.initials: F
authors.lastname: Er
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects*
chemical_list: D000889:Anti-Arrhythmia Agents