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Review
. 2019 May;8(2):105-110.
doi: 10.15420/aer.2019.1.1.

Long QT Syndrome Modelling with Cardiomyocytes Derived from Human-induced Pluripotent Stem Cells

Luca Sala  1 , Massimiliano Gnecchi  2   3 , Peter J Schwartz  1   4   5
Affiliations
Review

Long QT Syndrome Modelling with Cardiomyocytes Derived from Human-induced Pluripotent Stem Cells

Luca Sala et al. Arrhythm Electrophysiol Rev. 2019 May.

Abstract

Long QT syndrome (LQTS) is a potentially severe arrhythmogenic disorder, associated with a prolonged QT interval and sudden death, caused by mutations in key genes regulating cardiac electrophysiology. Current strategies to study LQTS in vitro include heterologous systems or animal models. Despite their value, the overwhelming power of genetic tools has exposed the many limitations of these technologies. In 2010, human-induced pluripotent stem cells (hiPSCs) revolutionised the field and allowed scientists to study in vitro some of the disease traits of LQTS on hiPSC-derived cardiomyocytes (hiPSC-CMs) from LQTS patients. In this concise review we present how the hiPSC technology has been used to model three main forms of LQTS and the severe form of LQTS associated with mutations in calmodulin. We also introduce some of the most recent challenges that must be tackled in the upcoming years to successfully shift hiPSC-CMs from powerful in vitro disease modelling tools into assets to improve risk stratification and clinical decision-making.

Keywords: Long QT syndrome; cardiac arrhythmias; cardiomyocytes; human-induced pluripotent stem cells; life-threatening arrhythmias; precision medicine; stem cells; sudden cardiac death.

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Conflict of interest statement

Disclosure: The authors have no conflicts of interest to declare.

Figures

Figure 1:
Figure 1:. Number of Human-induced Pluripotent Stem Cell Lines with Long QT Syndrome Mutations Published So Far in the Literature
Figure 2:
Figure 2:. Long QT Syndrome Generates Prolongation of QT Interval at the ECG, Action Potential Duration Measured with Patch Clamp and Field Potential Duration Recorded with Multielectrode Array
Figure 3:
Figure 3:. Effect of Beta-adrenergic Stimulation on Cardiomyocytes From Long QT Syndrome Type 1/Jervell and Lange-Nielsen Syndrome Patients
See this image and copyright information in PMC

References

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