Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells. Goßmann, M., Frotscher, R., Linder, P., Neumann, S., Bayer, R., Epple, M., Staat, M., Artmann, A., & Artmann, G., M. Cellular Physiology and Biochemistry, 38(3):1182-1198, 3, 2016.
Website doi abstract bibtex 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.
@article{
title = {Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells},
type = {article},
year = {2016},
keywords = {Cardiac myocytes,CellDrum,Heart tissue culture,Induced pluripotent stem cells,Inotropic compounds,Ion channels,Pharmacology},
pages = {1182-1198},
volume = {38},
websites = {http://www.ncbi.nlm.nih.gov/pubmed/26983082,http://www.karger.com/?doi=10.1159/000443124},
month = {3},
day = {17},
id = {bc36fb82-76ca-3f42-a60f-151214e179f7},
created = {2016-03-01T14:02:50.000Z},
file_attached = {false},
profile_id = {93ec0d5b-403c-3f87-b702-40b6362f05e6},
last_modified = {2020-03-12T21:46:59.930Z},
read = {false},
starred = {false},
authored = {true},
confirmed = {true},
hidden = {false},
citation_key = {Goßmann2016},
private_publication = {false},
abstract = {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.},
bibtype = {article},
author = {Goßmann, Matthias and Frotscher, Ralf and Linder, Peter and Neumann, Stephan and Bayer, Robin and Epple, Matthias and Staat, Manfred and Artmann, Aysegül and Artmann, Gerhard M.},
doi = {10.1159/000443124},
journal = {Cellular Physiology and Biochemistry},
number = {3}
}
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