title: Human embryonic and induced pluripotent stem cell-derived cardiomyocytes exhibit beat rate variability and power-law behavior.
abstract: BACKGROUND
  The sinoatrial node is the main impulse-generating tissue in the heart. Atrioventricular conduction block and arrhythmias caused by sinoatrial node dysfunction are clinically important and generally treated with electronic pacemakers. Although an excellent solution, electronic pacemakers incorporate limitations that have stimulated research on biological pacing. To assess the suitability of potential biological pacemakers, we tested the hypothesis that the spontaneous electric activity of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) exhibit beat rate variability and power-law behavior comparable to those of human sinoatrial node.
  
  
  RESULTS
  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 nonlinear dynamics. The major findings were that the mean beat rate of hESC-CMs and iPSC-CMs was stable throughout the 15-day follow-up period and was similar in both cell types, that hESC-CMs and iPSC-CMs exhibited intrinsic beat rate variability and fractal behavior, and that isoproterenol increased and carbamylcholine decreased the beating rate in both hESC-CMs and iPSC-CMs.
  
  
  CONCLUSIONS
  This is the first study demonstrating that hESC-CMs and iPSC-CMs exhibit beat rate variability and power-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 keratinocyte-derived iPSCs), thus eliminating the critical need for immunosuppression, renders these myocytes an attractive cell source as biological pacemakers.
authors.affiliation: Department of Physiology, Ruth and Bruce Rappaport Faculty of Medicine, PO Box 9649, Haifa, 31096 Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Mandel
authors.forename: Amir
authors.initials: A
authors.lastname: Weissman
authors.forename: Revital
authors.initials: R
authors.lastname: Schick
authors.forename: Lili
authors.initials: L
authors.lastname: Barad
authors.forename: Atara
authors.initials: A
authors.lastname: Novak
authors.forename: Gideon
authors.initials: G
authors.lastname: Meiry
authors.forename: Stanislav
authors.initials: S
authors.lastname: Goldberg
authors.forename: Avraham
authors.initials: A
authors.lastname: Lorber
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rosen
authors.forename: Joseph
authors.initials: J
authors.lastname: Itskovitz-Eldor
authors.forename: Ofer
authors.initials: O
authors.lastname: Binah
mesh_terms: D002217:Carbachol / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000166:cytology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D007545:Isoproterenol / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000502:physiology*; D012849:Sinoatrial Node / Q000502:physiology
chemical_list: D002217:Carbachol; D007545:Isoproterenol