Abstract 11679: Human Embryonic and Induced Pluripotent Stem Cells-Derived Cardiomyocytes Automaticity Exhibit Beat Rate Variability and Power-Law Behavior
Background: The sinoatrial node is the main impulse-generating tissue in the heart. Atrioventricular conduction block and/or arrhythmias caused by sinoatrial node dysfunction are clinically important and generally treated with electronic pacemakers. While an excellent solution, electronic pacemakers incorporate limitations that have stimulated research on biological pacing. To assess suitability of potential biological pacemakers, we tested the hypothesis that the spontaneous electrical activity of human embryonic stem cells derived cardiomyocytes (hESC-CM) and induced pluripotent stem cells derived cardiomyocytes (iPSC-CM) exhibit beat rate variability (BRV) and power-law behavior comparable to those of human sinoatrial node.
Methods and Results: To this end we recorded extracellular electrograms from hESC-CM and iPSC-CM under stable conditions for up to 15 days. The beat rate time series of the spontaneous activity were examined in terms of their power spectral density and additional methods derived from non-linear dynamics. The major findings were: (1) the mean beat rate of hESC-CM and iPSC-CM was stable throughout the 15-day follow-up period, and similar in both cell types. (2) hESC-CM and iPSC-CM exhibited intrinsic BRV and fractal behavior.
Conclusions: Collectively, this is the first study demonstrating that hESC-CM and iPSC-CM exhibit BRV and fractal behavior as in humans, thus supporting the capability of these cell sources to serve as biological pacemakers. Our ability to generate sinoatrial-compatible spontaneous cardiomyocytes from the patient's own hair (via keratinocytes-derived iPSC), thus eliminating the critical need for immunosuppression, renders these myocytes an attractive cell source as biological pacemakers.
- © 2011 by American Heart Association, Inc.