Disease modeling of cardiac arrhythmias using human induced pluripotent stem cells

Expert Opin Biol Ther. 2019 Apr;19(4):313-333. doi: 10.1080/14712598.2019.1575359. Epub 2019 Feb 7.

Abstract

Introduction: Inherited arrhythmias are an uncommon, but malignant family of cardiac diseases that result from genetic abnormalities in the ion channels and/or structural proteins within cardiomyocytes. Given the inherent differences between species and the limited reproducibility of in vitro heterologous cell models, progress in understanding the mechanisms underlying these malignant diseases has always languished far behind the clinical science and need. The ability to study human induced pluripotent stem cells (iPSCs) derived cardiomyocytes promises to change this paradigm as patient cells have the potential to become testing platforms for disease phenotyping or therapeutic discovery.

Areas covered: This review will outline methods developed to genetically reprogram adult cells into iPSCs, differentiate iPSCs into ex vivo models of adult cardiac tissue and iPSCs-based progress in exploring the mechanisms underlying pro-arrhythmic disease phenotypes.

Expert opinion: Despite being discovered less than 15 years ago, several studies have successfully leveraged iPSCs-derived cardiomyocytes to study malignant arrhythmogenic diseases. These models promise to increase our understanding of the pathophysiology underlying these complex diseases and may identify personalized approaches to treatment.

Keywords: Induced pluripotent stem cell; cardiac arrhythmia; cardiac electrophysiology; cell model; genetics; sudden death.

Publication types

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

MeSH terms

  • Arrhythmias, Cardiac / pathology
  • Arrhythmias, Cardiac / therapy*
  • Brugada Syndrome / therapy
  • Cell Differentiation
  • Cellular Reprogramming
  • Electric Stimulation
  • Genetic Vectors / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / transplantation*
  • Long QT Syndrome / therapy
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism