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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.
Our specialists are here to help you find the best product for your application.
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Our specialists are here to help you find the best product for your application.
Our regular business hours are 9:00am to 5:00pm Central Time (USA)
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
Figure 1: Structure of 3D Cardiac Tri-culture Microtissues Over Time.
Microtissues were formed containing 5,000 or 10,000 total cells in S-bio 96-well plates. Compact, contracting microtissues were obtained by Day 4. (A) Panel of phase contrast 10X images of 5,000 cell tri-culture spheroids over time using the Incucyte S3. (B) Quantification of 5,000 cell tri-culture microtissue diameter. Each dot represents a microtissue. Mean and SEM are indicated. (C) Comparison of Day 14 microtissue diameter of 5,000 cell tri-culture microtissues with 10,000 cell tri-culture microtissues. Each dot represents a microtissue. Mean and SEM are indicated. (D) H&E staining of Day 14, 3D cardiac tri-culture microtissue formed with 10,000 total cells. Staining shows the absence of a necrotic core.
Figure 2: 3D Cardiac Tri-culture Microtissues Response to Beta Adrenergic Agonist Isoproterenol
(A) Chronotropic response: Control iCell Cardiomyocytes, 11713 only microtissues (CM) and tri-culture microtissues exhibit an increase in beat rate with increasing concentrations of isoproterenol. (B) Inotropic response: Control iCell Cardiomyocytes, 11713 only microtissues (CM) do not increase amplitude with increasing concentrations of isoproterenol. Tri-culture microtissues demonstrate a twofold increase in beat amplitude with increasing concentrations of isoproterenol.
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
Figure 3: Baseline Calcium Transients in Cardiomyocyte and Tri-culture Microtissues at Day 14
Calcium transients were measured using EarlyTox calcium dye. (A) Representative calcium traces for 5,000 and 10,000 total cell 3D Tri-culture cardiac microtissues. (B) Beat rate is not different between 5,000 or 10,000 cell triculture microtissues and control cardiomyocyte only microtissues. (C) Representative calcium traces for 5,000 cell tri-culture and 5,000 cell cardiomyocytes only microtissues (CM only). (C) Amplitude is significantly higher in triculture microtissue compared to cardiomyocyte only microtissues (CM only) at 5,000 cells, but similar at 10,000 cells
Figure 4: iCell Cardiomyocytes Recapitulate Native Cardiac Function
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.
Figure 5: iCell Cardiomyocytes have Appropriate Sarcomeric Organization, Calcium Handling and Intact Excitation-Contraction Coupling.
Figure 6: Intracellular Calcium (Ca2+) Handling Provides a High-throughput Biomarker for Ion Channel and GPCR Activity.
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.
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).
Figure 7: iCell Cardiomyocytes are a High-Purity Cardiac Population.
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).
iCell Cardiomyocytes are compatible with bioengineered, implantable scaffolds used as a model for heart repair following myocardial infarction (Richards et al., 2017, Beauchamp et al., 2015, Holt-Casper et al., 2015, Lancaster et al., 2012).
Simultaneously assess effects on electrical and calcium signals measurements using iCell Cardiomyocytes with FDSS ( Bedut et al., 2016) or FLIPR platforms.
iCell Cardiomyocytes can detect known and novel biomarkers and identify new targets for drug discovery and therapeutics research (Jones et al., 2015, Drawnel et al., 2014, Arrarwal et al., 2014,, Traister et al., 2014, Zhi et al., 2012).
iCell Cardiomyocytes are changing regulatory paradigms by providing a highly predictive model for detecting drug-induced arrhythmia (Guo et al., 2018).
Electronic Cigarette Extract Induced Toxic Effect in iPS-derived Cardiomyocytes Hesham Basma, Swetha Tatineni, Kajari Dhar, Fang Qiu, Stephen Rennard, Brian D. Lowes (2020) BMC Cardiovasc Disord. 20: 357. (2020)
Inhibition of RNA Helicase Activity Prevents Coxsackievirus B3-Induced Myocarditis in Human iPS Cardiomyocytes Yun SH, Shin HH, Ju ES, Lee YJ, Lim BK & Jeon ES (2020) Int. J. Mol. Sci. 21: 3041. (2020)
Selective Induction of Human Autonomic Neurons Enables Precise Control of Cardiomyocyte Beating Takayama Y, Kushige H, Akagi Y, Suzuki Y, Kumagai Y & Kida YS (2020) Scientific Reports 10: 9464 (2020)
Detection of Drug-Induced Torsades de Pointes Arrhythmia Mechanisms Using hiPSC-CM Syncytial Monolayers in a High-Throughput Screening Voltage Sensitive Dye Assay da Rocha AM, Creech J, Thonn E, Mironov S, Herron TJ (2020) Toxicol Sci. 173(2):402-415 (2020)
Multiplexed Optical Sensors in Arrayed Islands of Cells for Multimodal Recordings of Cellular Physiology Christopher A. Werley, Stefano Boccardo, Alessandra Rigamonti, Emil M. Hansson & Adam E. Cohen (2020) Nature Comm. 11: 3881. (2020)
Assessing SSRIs' Effects on Fetal Cardiomyocytes Utilizing Placenta-Fetus Model Arumugasaamy N, Hurley-Novatny A, Lembong J, Kim PCW, Fisher JP. (2019) Acta Biomater. 99:258-268. (2019)
TGF-β Induces a Heart Failure Phenotype via Fibroblasts Exosome Signaling Basma H, Johanson AN, Dhar K, Anderson D, Qiu F, Rennard S, Lowes BD. (2019) Heliyon, 5:10, e02633. (2019)
Resolving the Reversed Rate Effect of Calcium Channel Blockers on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes and the Impact on in vitro Cardiac Safety Evaluation. Zeng H, Wang J, Clouse H, Lagrutta A, and Sannajust F. Toxicol Sci. (2019) 167(2):573-580. (2019)
Inhibitory Effects of Class 1 Antiarrhythmic Agents on Na+ and Ca2+ Currents of Human iPS Cell-derived Cardiomyocytes Yonemizu S, Masuda K, Kurata Y, Notsu T, Higashi Y, Fukumura K, Li P, Ninomiya H, Miake J, Tsuneto M, Shirayoshi Y, Hisatomea I (2019) Regen Ther 10: 104–111. (2019)
Human Cardiac Organoids for the Modeling of Myocardial Infarction and Drug Cardiotoxicity Richards DJ, Li Y, Kerr CM, Yao J, Beeson GC, Coyle RC, Chen X, Jia J, Damon B, Wilson R, Starr Hazard E, Hardiman G, Menick DR, Beeson CC, Yao H, Ye T, Mei Y (2020) Nat Biomed Eng. 4(4):446-462. (2020)