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Treatment of Patients with Long-QT Syndrome: Differentiation of Patient-Derived Induced Pluripotent Stem Cells into Functional Cardiac Myocytes

  • Daniel Sinnecker
  • Tatjana Dorn
  • Ralf J. Dirschinger
  • Alexander Goedel
  • Alessandra Moretti
  • Karl-Ludwig Laugwitz
Chapter
Part of the Stem Cells and Cancer Stem Cells book series (STEM, volume 9)

Abstract

The long-QT syndrome, which can be inherited (e.g. due to mutations in genes encoding cardiac ion channels) or acquired (e.g. due to the application of certain drugs), is characterized by a prolonged QT interval in the ECG which is caused by prolonged action potentials of single cardiomyocytes. Affected patients are susceptible to ventricular arrhythmias like torsades de pointes, which lead to palpitations, syncopes, or even sudden cardiac death. Induced pluripotent stem cell lines generated from skin fibroblasts of patients affected by congenital long-QT syndromes can be ­differentiated to cardiomyocytes, in which the pathophysiology of the disease can be studied in vitro. These patient-specific cardiomyocytes recapitulate typical features of the disease like a prolonged action potential duration, a defect of the physiological shortening of the action potential duration under conditions of increased heart rate, and a susceptibility to arrhythmogenic early afterdepolarizations. Moreover, the therapeutic effect of beta receptor antagonists can be recapitulated in vitro in these cells. Such patient-specific induced pluripotent stem cell models of the long-QT syndrome might be used in the future to screen for new drugs, to avoid unwanted drug side effects, and to individualize drug therapy.

Keywords

Action Potential Duration iPSC Line Cardiac Action Potential Delay Rectifier Potassium Current Catecholamine Stimulation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Daniel Sinnecker
    • 1
  • Tatjana Dorn
    • 1
  • Ralf J. Dirschinger
    • 1
  • Alexander Goedel
    • 1
  • Alessandra Moretti
    • 1
  • Karl-Ludwig Laugwitz
    • 1
  1. 1.Cardiology Division, First Department of Medicine and German Heart Center Munich, Kilinikim recht der IsarTechnological University of MunichMunichGermany

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