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 JF - 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 U6 - http://dx.doi.org/10.1159/000443124 SN - 1421-9778 (Online) SN - 1015-8987 (Print) VL - 38 IS - 3 SP - 1182 EP - 1198 PB - Karger CY - Basel ER - TY - PAT A1 - Artmann, Gerhard A1 - Linder, Peter A1 - Bayer, Robin A1 - Gossmann, Matthias T1 - Celldrum electrode arrangement for measuring mechanical stress [Patent of invention] N2 - The invention pertains to a CellDrum electrode arrangement for measuring mechanical stress, comprising a mechanical holder (1 ) and a non-conductive membrane (4), whereby the membrane (4) is at least partially fixed at its circumference to the mechanical holder (1), keeping it in place when the membrane (4) may bend due to forces acting on the membrane (4), the mechanical holder (1) and the membrane (4) forming a container, whereby the membrane (1) within the container comprises an cell- membrane compound layer or biological material (3) adhered to the deformable membrane 4 which in response to stimulation by an agent may exert mechanical stress to the membrane (4) such that the membrane bending stage changes whereby the container may be filled with an electrolyte, whereby an electric contact (2) is arranged allowing to contact said electrolyte when filled into to the container, whereby within a predefined geometry to the fixing of the membrane (4) an electrode (7) is arranged, whereby the electrode (7) is electrically insulated with respect to the electric contact (2) as well as said electrolyte, whereby mechanical stress due to an agent may be measured as a change in capacitance. Y1 - 2017 N1 - Patent auch unter EP3403090, CN109477828, US2019033245 und LU92948 veröffentlicht. PB - WIPO CY - Geneva ER -