Journal
BIOSENSORS & BIOELECTRONICS
Volume 124, Issue -, Pages 129-135Publisher
ELSEVIER ADVANCED TECHNOLOGY
DOI: 10.1016/j.bios.2018.10.021
Keywords
Excitation-contraction coupling; Human pluripotent stem cells; Cardiomyocytes; Atomic force microscopy; Microelectrode array; Drug testing
Categories
Funding
- Ministry of Education, Youth and Sports of the Czech Republic [LQ1601, LQ1605]
- CIISB research infrastructure project [LM2015043]
- Grant Agency of the Czech Republic (GACR) [P302/12/G157]
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Cardiomyocytes (CM) placed on microelectrode array (MEA) were simultaneously probed with cantilever from atomic force microscope (AFM) system. This electric / nanomechanical combination in real time recorded beating force of the CMs cluster and the triggering electric events. Such organ-on-a-chip represents a tool for drug development and disease modeling. The human pluripotent stem cells included the WT embryonic line CCTL14 and the induced dystrophin deficient line reprogrammed from fibroblasts of a patient affected by Duchenne Muscular Dystrophy (DMD, complete loss of dystrophin expression). Both were differentiated to CMs and employed with the AFM/MEA platform for diseased CMs' drug response testing and DMD characterization. The dependence of cardiac parameters on extracellular Ca2+ was studied. The differential evaluation explained the observed effects despite variability of biological samples. The beta-adrenergic stimulation (isoproterenol) and antagonist trials (verapamil) addressed ionotropic and chronotropic cell line-dependent features. For the first time, a distinctive beating-force relation for DMD CMs was measured on the 3D cardiac in vitro model.
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