Electrical Coupling of Cardiac Myocyte Cell Sheets to the Heart

Abstract

See related article, pages 705–712 The past 20 years have seen tremendous progress in the medical treatment of cardiac diseases, a progress that actually translated into decreased cardiovascular morbidity and mortality in clinical practice.1 Yet evidence accumulates that interventions intended to slow down the progression of chronic heart diseases have approached their limit. This may be one of the reasons why the recent progress in stem cell biology has stirred so much attention. In addition, recent studies suggesting the existence of cell populations in the adult organism that, albeit at a low rate and insufficiently, endogenously replace cardiac myocytes and endothelial and smooth muscle cells have challenged the dogma of the heart as a nonregenerating organ.2–5 Such cell populations could be accessed in biopsies and principally serve as a source to replace cardiac myocytes and other cardiac cell types lost after myocardial infarction or other pathologies. Human embryonic stem cell lines, on the other hand, can nowadays be generated from human blastocysts (accessible from IVF leftovers6) at a high success rate and have been unambiguously shown to generate human cardiac myocytes.7–9 Thus, despite many open questions and some controversy in the field (reviews in references 10,11), cardiac regenerative therapy has become a realistic perspective. But what to do with stem cells or their derivatives, given that means will be provided to generate them at sufficient numbers? The most straightforward strategy is to infuse or inject these cells into the injured heart and to develop methods to increase the fraction of cells that home and survive in the heart and differentiate to the desired functional elements. This strategy has already been clinically evaluated, but gave mixed results,12–16 potentially also because the homing rate after infusion and the survival rate after intramyocardial injections are very low. …