Human iPSC-Derived Cardiomyocytes for Investigation of Disease Mechanisms and Therapeutic Strategies in Inherited Arrhythmia Syndromes: Strengths and Limitations

Human iPSC-Derived Cardiomyocytes for Investigation of Disease Mechanisms and Therapeutic... During the last two decades, significant progress has been made in the identification of genetic defects underlying inherited arrhythmia syndromes, which has provided some clinical benefit through elucidation of gene-specific arrhythmia triggers and treatment. However, for most arrhythmia syndromes, clinical management is hindered by insufficient knowledge of the functional consequences of the mutation in question, the pro-arrhythmic mechanisms involved, and hence the most optimal treatment strategy. Moreover, disease expressivity and sensitivity to therapeutic interventions often varies between mutations and/or patients, underlining the need for more individualized strategies. The development of the induced pluripotent stem cell (iPSC) technology now provides the opportunity for generating iPSC-derived cardiomyocytes (CMs) from human material (hiPSC-CMs), enabling patient- and/or mutation-specific investigations. These hiPSC-CMs may furthermore be employed for identification and assessment of novel therapeutic strategies for arrhythmia syndromes. However, due to their relative immaturity, hiPSC-CMs also display a number of essential differences as compared to adult human CMs, and hence there are certain limitations in their use. We here review the electrophysiological characteristics of hiPSC-CMs, their use for investigating inherited arrhythmia syndromes, and their applicability for identification and assessment of (novel) anti-arrhythmic treatment strategies. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cardiovascular Drugs and Therapy Springer Journals

Human iPSC-Derived Cardiomyocytes for Investigation of Disease Mechanisms and Therapeutic Strategies in Inherited Arrhythmia Syndromes: Strengths and Limitations

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Publisher
Springer US
Copyright
Copyright © 2017 by The Author(s)
Subject
Medicine & Public Health; Cardiology
ISSN
0920-3206
eISSN
1573-7241
D.O.I.
10.1007/s10557-017-6735-0
Publisher site
See Article on Publisher Site

Abstract

During the last two decades, significant progress has been made in the identification of genetic defects underlying inherited arrhythmia syndromes, which has provided some clinical benefit through elucidation of gene-specific arrhythmia triggers and treatment. However, for most arrhythmia syndromes, clinical management is hindered by insufficient knowledge of the functional consequences of the mutation in question, the pro-arrhythmic mechanisms involved, and hence the most optimal treatment strategy. Moreover, disease expressivity and sensitivity to therapeutic interventions often varies between mutations and/or patients, underlining the need for more individualized strategies. The development of the induced pluripotent stem cell (iPSC) technology now provides the opportunity for generating iPSC-derived cardiomyocytes (CMs) from human material (hiPSC-CMs), enabling patient- and/or mutation-specific investigations. These hiPSC-CMs may furthermore be employed for identification and assessment of novel therapeutic strategies for arrhythmia syndromes. However, due to their relative immaturity, hiPSC-CMs also display a number of essential differences as compared to adult human CMs, and hence there are certain limitations in their use. We here review the electrophysiological characteristics of hiPSC-CMs, their use for investigating inherited arrhythmia syndromes, and their applicability for identification and assessment of (novel) anti-arrhythmic treatment strategies.

Journal

Cardiovascular Drugs and TherapySpringer Journals

Published: Jul 18, 2017

References

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