The Advantages, Challenges, and Future of Human-Induced Pluripotent Stem Cell Lines in Type 2 Long QT Syndrome

J Cardiovasc Transl Res. 2023 Feb;16(1):209-220. doi: 10.1007/s12265-022-10298-x. Epub 2022 Aug 17.

Abstract

Type 2 long QT syndrome (LQT2) is the second most common subtype of long QT syndrome and is caused by mutations in KCHN2 encoding the rapidly activating delayed rectifier potassium channel vital for ventricular repolarization. Sudden cardiac death is a sentinel event of LQT2. Preclinical diagnosis by genetic testing is potentially life-saving.Traditional LQT2 models cannot wholly recapitulate genetic and phenotypic features; therefore, there is a demand for a reliable experimental model. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) meet this challenge. This review introduces the advantages of the hiPSC-CM model over the traditional model and discusses how hiPSC-CM and gene editing are used to decipher mechanisms of LQT2, screen for cardiotoxicity, and identify therapeutic strategies, thus promoting the realization of precision medicine for LQT2 patients.

Keywords: Gene editing; Human-induced pluripotent stem cells; KCNH2; Precision medicine; Type 2 long QT syndrome.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • ERG1 Potassium Channel / genetics
  • ERG1 Potassium Channel / metabolism
  • Genetic Testing
  • Humans
  • Induced Pluripotent Stem Cells* / metabolism
  • Long QT Syndrome* / drug therapy
  • Long QT Syndrome* / genetics
  • Mutation
  • Myocytes, Cardiac / metabolism

Substances

  • ERG1 Potassium Channel