Cardiac Repolarization and Stem Cells: An Emerging Path Toward Precision Medicine

The discovery of a genetic basis for cardiac repolarization disorders has introduced innovative technologies and concepts in the field of cardiac arrhythmias and has revolutionized the knowledge of these disorders as well as patients’ treatment. Conventional methodologies for the in vitro study of cardiac arrhythmias, only indirectly linked to the clinical phenotype, have started to age, and the information they can now provide suddenly appears limited. After the discovery that patient-specific cardiomyocytes can be derived, in virtually unlimited numbers, from pluripotent stem cells, we are now on the edge of another breakthrough with basic science laboratories heavily linked to clinical practice and offering tools with substantially higher translational capabilities. In this chapter, we present an excursus on the path that has led to the discovery, optimization, and implementation of pluripotent stem cell-derived cardiomyocytes for cardiac disease modeling. Then, we cover the major repolarization disorders with genetic bases whose phenotypes have been recapitulated and studied with these cardiomyocytes. Along this, we describe the techniques currently used to study repolarization disorders in vitro, and we offer a glimpse on what will come next in this field. Finally, we analyze the translational relevance of the powerful combination between genetics and stem cell-based approaches for cardiac arrhythmias, in a context of precision medicine.