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Heart disease encompasses a wide range of conditions that can be a result of genetics, physiologic, and metabolic disorders as well as adverse drug reactions. The availability of human cell models that could be used to interrogate these various factors would have a profound impact on the effort to find new medicines and cures for heart disease. Derived from induced pluripotent stem cells (iPSCs), iCell® Cardiomyocytes from FUJIFILM Cellular Dynamics, Inc. (FCDI), enable a wide range of applications spanning disease research, drug discovery, safety and toxicity testing, and regenerative medicine.
Three-dimensional multi-cellular systems containing iCell Cardiomyocytes or iCell Cardiomyocytes2, iCell Endothelial Cells and primary cardiac fibroblasts have the potential for greater physiological relevance, predictive power, and mechanistic insight than cardiomyocytes alone. For information on 3D systems, see the Application Protocol: Culturing and Assaying Calcium Transients of 3D Cardiac Tri-Culture Microtissues
3D cardiac tri-culture microtissues containing iCell Cardiomyocytes or iCell Cardiomyocytes2, iCell Endothelial Cells and cardiac fibroblasts demonstrated a positive response to the inotropic compound isoproterenol, which is characteristic of mature cardiomyocytes. For information on 3D triculture systems, see the Application Protocol: Culturing and Assaying Calcium Transients of 3D Cardiac Tri-Culture Microtissues
Three-dimensional multi-cellular systems containing iCell Cardiomyocytes or iCell Cardiomyocytes2, iCell Endothelial Cells and cardiac fibroblasts demonstrate enhanced amplitude in calcium transient assays. For information on 3D systems, see the Application Protocol: Culturing and Assaying Calcium Transients of 3D Cardiac Tri-Culture Microtissues
Flow cytometry analysis and immunostaining show that iCell Cardiomyocytes are typically >95% cTNT+) with intact sarcomeric myofilament organization. (Data were adapted from Kattman et al., 2011).
iCell Cardiomyocytes form a spontaneously beating monolayer within 7 days. iCell Cardiomyocytes contain the expected human cardiac ionic currents and show the expected effects when exposed to compounds including ion channel blockers. (Data were adapted from Ma et al., 2011).
Their electrophysiological activity can be pharmacologically modulated and quantified by recording the electrical activity using a multielectrode array (MEA). The field potential duration (FPD) increases or decreases as expected when exposed to ion channel-blocking drugs for key cardiac channels.
Electrical activity at the membrane is controlled by ion channels and GPCRs. This activity drives intracellular Ca2+ handling. Panel A shows representative calcium handling waveforms at baseline. Panels B and C show the effect of the GPCR β-adrenergic agonist ISO or the IKr channel blocker E-4031, respectively.
Simultaneously assess effects on electrical and calcium signals measurements using iCell Cardiomyocytes with FDSS ( Bedut et al., 2016) or FLIPR platforms.
Retrospective analyses were leveraged to uncover previously undetected mechanisms of drug-induced cardiotoxicity and provide relevant data in support of Investigational New Drug (IND) applications (Talbert et al., 2014, Cameron et al., 2013, Doherty et al., 2013, Rana et al., 2012, Cohen et al., 2011).