Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 38, Issue 3, Pages 1182-1198Publisher
KARGER
DOI: 10.1159/000443124
Keywords
Cardiac myocytes; Induced pluripotent stem cells; Heart tissue culture; CellDrum; Ion channels; Pharmacology; Inotropic compounds
Categories
Funding
- EFRE
- State Ministry of Economic Affairs, Energy and Industry of North Rhine-Westphalia, Germany [FKZ: 005-1009-0058]
- Ministry of Innovation, Science and Research of the State of North Rhine-Westphalia [1403ts021]
Ask authors/readers for more resources
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-BayyK8644/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 doseresponse 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. (C) 2016 The Author(s) Published by S. Karger AG, Basel
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available