Induced pluripotent stem cells as cardiac arrhythmic in vitro models and the impact for drug discovery

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords::

• antiarrhythmic drugs
• cardiac arrhythmia
• cardiomyocyte
• cell-based assay
• differentiation
• drug attrition
• electrophysiology
• in vitro disease modeling
• induced pluripotent stem cells
• inherited diseases
• ion channel
• reprogramming

Notes

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