Assessment of Proarrhythmic Potential
Using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is an accurate and useful method for predicting the proarrhythmic potential of drug candidates. This method is listed in the ICH Guidelines (S7B/E14) Q&A as a follow-up study. FUJIFILM has been dedicated to developing an assay that can generate high-quality data in a 96-well format with excellent reliability. Consequentl, FUJIFILM offers a rapid and precise assay service for the evaluation of proarrhythmic potential of candidate compounds in the field of drug discovery.
Acquisition of High-Quality Extracellular Field Potential
Cell culture protocol for high-quality extracellular field potential.
Criteria to control data quality.
- Signal amplitude (1st peak, 2nd peak)
- Shape of the wave form
(depolarization to repolarization)
Dose Response
Report
22 cmps in 1 plate for High-Throughput Evaluation
Standard Protocol：4 doses with cumulative addition, Quadruple
Propriate Cell Culture Protocol to Achieve High-Quality Data with fewer Electrodes.
iCell® Cardiomyocytes2
iCell® Cardiomyocytes2 is a Human-induced pluripotent stem cell-derived cardiomyocytes that closely resemble the functions of human cardiomyocytes.
iCell® Cardiomyocytes2 is a Valuable Tool for Pharmacology, Safety Pharmacology and Research for Cell Functions with Various Assay Platforms.
Basic Property as Cardiomyocytes
Ma et al., Am J Physiol Heart Circ Physiol 30 (2011) H2006-H2017
Expression of Ion Channels
Kodama et al., J Pharmacol. Sci. 140 (2019) 325-330
iCell® Cardiomyocytes2 is a high-purity cardiomyocyte derived from human-induced pluripotent stem cells (hiPSCs) produced by FUJIFILM Cellular Dynamics, Inc. with propriate differentiation and purification technologies. Atrial, nodular, and ventricular cardiomyocytes with spontaneous electrical activity possess typical biochemical, electrophysiological, and mechanical properties as cardiomyocytes, as well as higher expression levels of marker-genes, including ion-channels, compared to hiPSC-derived cardiomyocytes from other companies.
Typical Assay Plan and Background Data
We have developed a propriate cell culture protocol to ensure precise cell coverage on electrodes. This protocol enables the acquisition of high-quality extracellular field potential data that satisfies the analysis criteria for all wells in 96-well format. Furthermore, it allows for the evaluation of the proarrhythmic potential of 22 compounds at 4 different doses per plate.
Example
Controls Positive：E-4031 Vehicle： DMSO
N=4 22 cmps
4 doses for each compound with cumulative addition
Dose response of FPDc change
Results of CiPA compounds1
1. Blinova et al., Cell Reports 24 (2018) 3582-3592
Robustness of drug response
2. Kitaguchi et al., J Pharmacological and Toxicological Methods 78 (2016) 93-102
3. Nozaki et al., Regulatory Toxicology and Pharmacology 77 (2016) 75-86
Prolongation and shortening of FPDc, as well as proarrhythmic effects, were accurately detected.
The concentration range of the effects has been verified to be consistent with previous reports.
Service Flow
MEA system (Axion BioSystems, Inc.）
- Maestro Pro and Cytoview MEA plate
Cells and regents (FUJIFILM Cellular Dynamics, Inc.）
- Cells: iCell® Cardiomyocytes2
- Media: iCell® CM Plating Medium, iCell® CM Maintainance Medium
End Point
- FPD/FPDc
- Proarrhythmic Potential
(Occurrence of EAD, Cardiac Arrest, Abnormal) - Beat Rate
For research use or further manufacturing use only. Not for use in diagnostic procedures.
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