TY  - JOUR
A1  - Goßmann, Matthias
A1  - Frotscher, Ralf
A1  - Linder, Peter
A1  - Bayer, Robin
A1  - Epple, U.
A1  - Staat, Manfred
A1  - Temiz Artmann, Aysegül
A1  - Artmann, Gerhard
T1  - Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells
T2  - Cellular physiology and biochemistry
N2  - 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.
KW  - Inotropic compounds
KW  - Pharmacology
KW  - Ion channels
KW  - CellDrum
KW  - Heart tissue culture
KW  - Induced pluripotent stem cells
KW  - Cardiac myocytes
Y1  - 2016
UR  - https://opus.bibliothek.fh-aachen.de/opus4/frontdoor/index/index/docId/7622
SN  - 1421-9778 (Online)
SN  - 1015-8987 (Print)
VL  - 38
IS  - 3
SP  - 1182
EP  - 1198
PB  - Karger
CY  - Basel
ER  -