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Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells

  • Background/Aims: 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. Conclusion: 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.

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Metadaten
Author:Matthias GoßmannORCiD, Ralf FrotscherORCiD, Peter LinderORCiD, Robin BayerORCiD, U. Epple, Manfred StaatORCiD, Aysegül Temiz ArtmannORCiD, Gerhard ArtmannORCiD
DOI:https://doi.org/10.1159/000443124
ISSN:1421-9778 (Online)
ISSN:1015-8987 (Print)
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=26983082
Parent Title (English):Cellular physiology and biochemistry
Publisher:Karger
Place of publication:Basel
Document Type:Article
Language:English
Year of Completion:2016
Date of the Publication (Server):2016/03/02
Tag:Cardiac myocytes; CellDrum; Heart tissue culture; Induced pluripotent stem cells; Inotropic compounds; Ion channels; Pharmacology
Volume:38
Issue:3
First Page:1182
Last Page:1198
Link:http://dx.doi.org/10.1159/000443124
Zugriffsart:weltweit
Institutes:FH Aachen / Fachbereich Medizintechnik und Technomathematik
FH Aachen / IfB - Institut für Bioengineering
collections:Verlag / Karger
Open Access / Gold