Abstract
Promising pharmaceuticals frequently fail clinical trials due to cardiotoxicity or a decline in heart function not indicated from preclinical animal models and in vitro tests. The development of low-cost, high-throughput, and reliable in vitro human models remains a priority for pharmaceutical companies to avoid costly dead ends in clinical trials. Organ-on-a-chip systems allow the creation of functional, human tissue test beds that leverage the benefits of miniaturization using Biomicroelectromechanical System (BioMEMS) devices and the availability of differentiable human stem cells.
We have developed a 2D cardiac platform that allows the functional interrogation of human embryonic stem cell (hESC)-derived cardiomyocytes. The platform uses a laser to reflect off silicon cantilevers with adhered cardiomyocytes to monitor the contraction-induced deflection, enabling the calculation of contractile force.
Chips with up to 32 cantilevers can be scanned by an automated stage sending the cardiac signals to a high-speed detector that can record the spatial coordinates and transform them into force output. Separately, electrical conduction can also be monitored by patterning cardiomyocytes on top of microelectrode arrays. This platform enables physiologic characterization of inherited cardiomyopathies, as well as acute and chronic drug studies with arrhythmogenic and inotropic compounds, to predict their effect on in vivo cardiac output, as well as general toxicological evaluations.
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Oleaga, C. et al. (2017). Contractile Force Readout of hESC-Cardiomyocytes. In: Clements, M., Roquemore, L. (eds) Stem Cell-Derived Models in Toxicology. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6661-5_12
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DOI: https://doi.org/10.1007/978-1-4939-6661-5_12
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