Key result
The CellDrum technology combined with hiPS-CMs accurately measured pharmacological dose-response curves for Ca2+ and Na+ channel modulators, consistent with reference data in native human heart tissue.
The combination of CellDrum technology with hiPS-CMs offers a precise and scalable system for preclinical pharmacological and toxicological testing of cellular mechanical tension.
Supports hiPS-CM platforms for preclinical screening; leaves open clinical translation pending further validation.
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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Goßmann et al. (2016) studied In vitro cardiomyocyte contraction. Ca2+ and Na+ channel agonists and antagonists (S-Bay K8644/verapamil, veratridine/lidocaine) vs. Unstimulated contraction was evaluated on Contraction-relaxation-cycles (amplitudes, durations, time integrals, frequencies, force, tensile stress). The CellDrum technology combined with hiPS-CMs accurately measured pharmacological dose-response curves for Ca2+ and Na+ channel modulators, consistent with reference data in native human heart tissue.
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