%0 Journal Article %1 Goßmann2016 %A Goßmann, Matthias %A Frotscher, Ralf %A Linder, Peter %A Neumann, Stephan %A Bayer, Robin %A Epple, Matthias %A Staat, Manfred %A Artmann, Aysegül %A Artmann, Gerhard M. %D 2016 %J Cellular Physiology and Biochemistry %K Cardiac cells,Inotropic channels,Pharmacology compounds,Ion culture,Induced myocytes,CellDrum,Heart pluripotent stem tissue %N 3 %P 1182--1198 %R 10.1159/000443124 %T Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells %U http://www.ncbi.nlm.nih.gov/pubmed/26983082 http://www.karger.com/?doi=10.1159/000443124 %V 38 %X 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{Goßmann2016, 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.}, added-at = {2019-12-23T09:34:32.000+0100}, author = {Go{\ss}mann, Matthias and Frotscher, Ralf and Linder, Peter and Neumann, Stephan and Bayer, Robin and Epple, Matthias and Staat, Manfred and Artmann, Ayseg{\"{u}}l and Artmann, Gerhard M.}, biburl = {https://www.bibsonomy.org/bibtex/20dea38ce48c92f7ce876bcdf9fd0d347/staat}, doi = {10.1159/000443124}, interhash = {8aab871983f7d4be1de3abbbff72299a}, intrahash = {0dea38ce48c92f7ce876bcdf9fd0d347}, issn = {14219778}, journal = {Cellular Physiology and Biochemistry}, keywords = {Cardiac cells,Inotropic channels,Pharmacology compounds,Ion culture,Induced myocytes,CellDrum,Heart pluripotent stem tissue}, month = mar, number = 3, pages = {1182--1198}, pmid = {26983082}, timestamp = {2019-12-23T09:34:32.000+0100}, title = {{Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells}}, url = {http://www.ncbi.nlm.nih.gov/pubmed/26983082 http://www.karger.com/?doi=10.1159/000443124}, volume = 38, year = 2016 }