Patient-specific induced pluripotent stem cells for cardiac disease modeling

Abstract

Reprogramming of human somatic cells to induced pluripotent stem cells (iPSCs) via induction of pluripotency genes is one of the most influential scientific breakthroughs during the last decade. Behind this breakthrough is the capacity of iPSCs to self-renew and differentiate into derivatives of all the three germ layers, similar to human embryonic stem cells. Importantly, iPSCs can be generated using somatic cells from healthy donors or patients retaining the genetic and epigenetic make-up of the donor and can be used for regenerative applications without provoking immune rejection. Given their potential use in basic and translational research, iPSCs have become an attractive cell type to create "disease-on-a-dish" models to investigate disease phenotype in vitro, to assess drug response and evaluate cardiac toxicity for drug discovery, and to develop personalized cell therapy for various diseases. Among these diseases, inherited or acquired forms of cardiovascular diseases are the most common reason of mortality worldwide. Cardiac arrhythmias and channelopathies are a distinct group of disorders caused by abnormal ion homeostasis and action potential of cardiomyocytes, accounting for a large subset of hospitalization and sudden cardiac death. Pharmacological, catheter, or medical device implants and surgical approaches have been largely applied in the clinical perspective for symptomatic treatment and to improve the quality of life for patients with arrhythmias and other heart diseases. Recently, stem-cell-based regenerative approaches have been vigorously assessed in clinical trials, and novel stem-cell-based treatments are being evaluated for their potential use to provide lasting recovery. In this book chapter, we focus on the recent progress in the application of iPSC-related research in selected channelopathies and cardiac arrhythmia modeling in vitro and their potential application in the clinical perspective.