Stem Cell Therapy Is Proarrhythmic

Stem cell therapy appears to be a promising modality for myocardial repair of both hearts that are post myocardial infarction (MI) and those with other forms of structural cardiac disease (eg, congestive heart failure). In fact, recent experimental and clinical work has suggested that stem cell therapy contributes to cardiac regeneration. Unfortunately at this time, we contend that stem cell therapy is proarrhythmic. Accordingly, in this review we will approach this subject by restating this potential in the framework of traditional mechanisms of arrhythmias (automaticity and reentry). Lastly, we will address recent clinical work with stem cells, commenting on the proarrhythmic outcomes. Before assessing the proarrhythmic potential of stem cells, we think it important to first address the nature of the players. After all, these “players” are the cells selected for use in trials. ### Embryonic Stem Cells Obviously, because this cell population has the capacity to develop into differentiated cardiac cells, these cells have been phenotyped in terms of ionic current makeup, intracellular Ca2+ handling, and connexin expression.1 Embryonic Stem Cells (ESCs) have been shown to have at least fast sodium current, L-type Ca2+ current, If, IK1,2,3 and immature excitation-contraction (EC) coupling.4 Thus, implanting them into damaged myocardium would mean implanting areas of additional excitable cells that presumably would form gap junctions not only with fellow ESCs but also with surviving myocytes of the damaged substrate. Evidence for resident cardiac stem cells5,6 has surfaced, and these excitable cells could show promise for use in stem cell therapy. For example, c-Kit+ cardiac-derived cells isolated from a normal rat heart when delivered via the aortic root seem to invade the infarcted myocardium and regenerate muscle to improve left ventricular (LV) function.7 Unfortunately, no mention was made of rhythm instability (or stability) of the injected …