CiPA Validation of Human iPSC-derived Cardiomyocytes Using MEA Recording – Assessment of 28 Blinded Compounds

Event Abstract Back to Event CiPA Validation of Human iPSC-derived Cardiomyocytes Using MEA Recording – Assessment of 28 Blinded Compounds Ralf F. Kettenhofen1*, Greg Luerman2 and Tessa De Korte3 1 Ncardia (Germany), Germany 2 Ncardia USA, United States 3 Ncardia (Netherlands), Netherlands Microelectrode array (MEA) recordings were part of the HESI/CSRC/FDA Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative to validate hiPSC-derived cardiomyocytes (hiPSCM) using 28 compounds with known clinical risk to induce Torsade des Pointes tachyarrhythmias (of high, medium or low risk). The data from these studies will be used to generate a statistical prediction model models to assess unknown compounds. Here we show our data from the all, recently unblinded 28 test compounds that were acquired on the Axion Maestro 96 well microelectrode array. In summary, the positive control, 3 nM Dofetilide, was strikingly reproducible as it produced a very consistent FPDc prolongation of 30% to 40% across all 7 MEA plates (with no EADs). Additionally, we show data from all 28 compounds, including FPD prolongation and quantified the number of wells eliciting pro-arrhythmic responses (early afterdepolarizations, tachycardia, etc). The results reveal the predictive value of hiPSCM to assess in vitro the risk of drug-induced Torsade des Pointes in the clinic. Figure 1 Keywords: Human Induced Pluripotent Stem Cells, CIPA, safety pharmacology, cardiomyocytes, Validation study, Microelectrode Array (MEA) Conference: MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays, Reutlingen, Germany, 4 Jul - 6 Jul, 2018. Presentation Type: Poster Presentation Topic: Stem cell-derived applications Citation: Kettenhofen RF, Luerman G and De Korte T (2019). CiPA Validation of Human iPSC-derived Cardiomyocytes Using MEA Recording – Assessment of 28 Blinded Compounds. Conference Abstract: MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays. doi: 10.3389/conf.fncel.2018.38.00071 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 18 Mar 2018; Published Online: 17 Jan 2019. * Correspondence: Dr. Ralf F Kettenhofen, Ncardia (Germany), Cologne, Germany, ralf.kettenhofen@ncardia.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Ralf F Kettenhofen Greg Luerman Tessa De Korte Google Ralf F Kettenhofen Greg Luerman Tessa De Korte Google Scholar Ralf F Kettenhofen Greg Luerman Tessa De Korte PubMed Ralf F Kettenhofen Greg Luerman Tessa De Korte Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.