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Ischemic heart disease remains a leading cause of mortality worldwide. Myocardial infarction (MI) accounts for more than half of cardiovascular-related deaths.1 With rising numbers of surviving MI patients and an aging population, congestive heart failure has become a major health concern, with symptomatic patients having a poorer prognosis.2 Despite substantial advances in medical and device strategies for congestive heart failure, there remains a growing unmet clinical need. Accordingly, various novel therapies have been explored in recent years, with the potential offered by stem cells (SCs) arguably garnering the most attention.3,4 Cardiac SC therapy has emerged as a promising option to repair ischemic/dysfunctional myocardium through a variety of potential mechanisms (Figure 1).5–7 Continuing debates over unresolved mechanistic issues and the rapid transition toward clinical application, with already-demonstrated modest but tangible benefits for cardiac structure and function, underscore the fact that the field is still in its infancy.8–10 As with other emerging therapies, safety concerns have arisen in relation to potential hazards of SC therapy.11 Figure 1. Postulated mechanisms for beneficial effects of cardiac SC therapy. SC therapy has been shown to increase cardiac performance. Both direct and indirect mechanisms (as listed in the Figure) have been proposed to explain this benefit. However, as illustrated by the schematic balance, the weight of currently available evidence suggests that indirect mechanisms are more important.Among the most contentious issues, the risk of proarrhythmia has sparked debate and generated lingering doubts, which run the risk of paralyzing a potentially revolutionary opportunity.12–15 Although findings that have raised concerns about proarrhythmic potential of SC transplants cannot be discounted, we contend that the available data are encouraging rather than damning. Here, we highlight experimental and clinical data on SC-related arrhythmogenesis, discuss possible confounding issues, and argue that SC therapy, rather …

Stem Cells Are Not Proarrhythmic: Letting the Genie out of the Bottle