Human Embryonic and Induced Pluripotent Stem Cells-Derived Cardiomyocytes 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 sinoatrialnode dysfunction are clinically important andgenerally treated with electronic pacemakers. While an excellent solution, electronic pacemakers incorporate limitations that have stimulated research onbiological 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-CMs) and induced pluripotent stem cells derived cardiomyocytes (iPSC-CMs) 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-CMs and iPSC-CMs 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-CMs and iPSC-CMs was stable throughout the 15-day follow-up period, and similar in both cell types. (2) hESC-CMs and iPSC-CMs exhibited intrinsic BRV and fractal behavior; (3) In both hESC-CMs and iPSC-CMs, isoproterenol increased and carbamylcholine decreased the beating rate.
Conclusions—Collectively, this is the first study demonstrating that hESC-CMs and iPSC-CMs exhibit BRV andpower law behavior as in humans, thus supporting the potential 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.
- Received May 24, 2011.
- Accepted December 12, 2011.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited