Induced pluripotent stem cell technology: Toward the future of cardiac arrhythmias

Cardiovascular genetic diseases are a major cause of morbidity and the leading cause of sudden cardiac death (SCD) in young subjects. Even though significant progresses have been made in the understanding of these genetic disorders, there are still several unanswered questions. So far, the major limitation for studying inherited cardiovascular diseases at cellular level has been the lack of patient-specific cardiomyocytes (CMs) since they cannot be easily obtained from patients and the in vitro and in vivo models currently available are often inadequate for the purpose. For instance, the ion channel machinery characterizing the Long QT Syndrome (LQTS) cannot be totally reproduced by current cell or mouse models. The paradigm-shift that followed the development of induced pluripotent stem cells (iPSCs) has changed both our perspective and research potential. Now, by simply collecting somatic cells from a patient, we can obtain CMs derived from the iPSCs (iPSC-CMs) of the same subject in just a few weeks. Several lines of evidence have suggested that iPSCs can be used for modeling inherited arrhythmogenic disorders and, perhaps, for developing personalized therapies for these life-threatening diseases. Here, we will briefly review the state-of-the-art in using iPSCs for the study of one of the best characterized arrhythmogenic disorder of genetic origin, LQTS, highlighting the results achieved so far and foreseeing the future outlooks and challenges of the field