title: Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells.
abstract: OBJECTIVE
  Common systems for the quantification of cellular contraction rely on animal-based models, complex experimental setups or indirect approaches. The herein presented CellDrum technology for testing mechanical tension of cellular monolayers and thin tissue constructs has the potential to scale-up mechanical testing towards medium-throughput analyses. Using hiPS-Cardiac Myocytes (hiPS-CMs) it represents a new perspective of drug testing and brings us closer to personalized drug medication.
  
  
  METHODS
  In the present study, monolayers of self-beating hiPS-CMs were grown on ultra-thin circular silicone membranes and deflect under the weight of the culture medium. Rhythmic contractions of the hiPS-CMs induced variations of the membrane deflection. The recorded contraction-relaxation-cycles were analyzed with respect to their amplitudes, durations, time integrals and frequencies. Besides unstimulated force and tensile stress, we investigated the effects of agonists and antagonists acting on Ca2+ channels (S-Bay K8644/verapamil) and Na+ channels (veratridine/lidocaine).
  
  
  RESULTS
  The measured data and simulations for pharmacologically unstimulated contraction resembled findings in native human heart tissue, while the pharmacological dose-response curves were highly accurate and consistent with reference data.
  
  
  CONCLUSIONS
  We conclude that the combination of the CellDrum with hiPS-CMs offers a fast, facile and precise system for pharmacological, toxicological studies and offers new preclinical basic research potential.
authors.forename: Matthias
authors.initials: M
authors.lastname: Goßmann
authors.forename: Ralf
authors.initials: R
authors.lastname: Frotscher
authors.forename: Peter
authors.initials: P
authors.lastname: Linder
authors.forename: Stephan
authors.initials: S
authors.lastname: Neumann
authors.forename: Robin
authors.initials: R
authors.lastname: Bayer
authors.forename: Matthias
authors.initials: M
authors.lastname: Epple
authors.forename: Manfred
authors.initials: M
authors.lastname: Staat
authors.forename: Ayşegül Temiz
authors.initials: AT
authors.lastname: Artmann
authors.forename: Gerhard M
authors.initials: GM
authors.lastname: Artmann
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D007473:Ion Channels / Q000819:agonists* / Q000037:antagonists & inhibitors*; D008012:Lidocaine / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D013314:Stress, Mechanical; D014700:Verapamil / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
chemical_list: D007473:Ion Channels; D014701:Veratridine; D008012:Lidocaine; D014700:Verapamil