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(Circulation. 2009;119:1814-1823.)
© 2009 American Heart Association, Inc.

Controversies in Cardiovascular Medicine

Is stem cell therapy proarrhythmic?

Stem Cell Therapy Is Proarrhythmic

Ester Macia, MD; Penelope A. Boyden, PhD

From the Department of Pharmacology, Center for Molecular Therapeutics, Columbia University, New York, NY.

Correspondence to Dr Penelope A. Boyden, Dept of Pharmacology, Columbia College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032. E-mail pab4@columbia.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
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.

	The Players

 
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, I_f, I_K1,^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 cells^5,6 has surfaced, and these excitable cells could show promise for use in stem cell therapy. For example, c-Kit+ cardiac-derived . . . [Full Text of this Article]

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