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Non-invasive electromechanical cell-based biosensors for improved investigation of 3D cardiac models

G. Caluori, J. Pribyl, M. Pesl, S. Jelinkova, V. Rotrekl, P. Skladal, R. Raiteri,

. 2019 ; 124-125 (-) : 129-135. [pub] 20181016

Language English Country England, Great Britain

Document type Journal Article

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 β-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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$a Caluori, Guido $u Central European Institute of Technology, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic; International Clinical Research Centre of Saint Anne Hospital Brno, Pekarska 53, 60200 Brno, Czech Republic; Department of Informatics, Bioengineering Robotics and Systems Engineering, University of Genova, Via All'Opera Pia, 13, 16145 Genova, Italy.
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$a 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 β-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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$a Pribyl, Jan $u Central European Institute of Technology, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic.
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$a Pesl, Martin $u International Clinical Research Centre of Saint Anne Hospital Brno, Pekarska 53, 60200 Brno, Czech Republic; Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic; 1st Department of Cardiovascular Diseases, St. Anne's University Hospital and Masaryk University, Pekarska 53, Brno, Czech Republic.
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$a Jelinkova, Sarka $u Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic.
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$a Rotrekl, Vladimir $u Department of Biology, Faculty of Medicine, Masaryk University, Kamenice 5, 62500 Brno, Czech Republic.
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$a Raiteri, Roberto $u Department of Informatics, Bioengineering Robotics and Systems Engineering, University of Genova, Via All'Opera Pia, 13, 16145 Genova, Italy. Electronic address: roberto.raiteri@unige.it.
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