Electrical activity of developing cardiomyocytes

Abstract

Event Abstract Back to Event Electrical activity of developing cardiomyocytes Saskia Wuttke1*, Gabriele Brockerhoff1, Laura Nimtz1, Julia Tigges1 and Ellen Fritsche1 1 Leibniz-Institut für umweltmedizinische Forschung (IUF), Modern Risk Assessment and Sphere Biology, Germany Today developmental toxicity testing is often performed on animals due to several guidelines (OECD, U.S. EPA , ). This method is time and resource-intensive resulting in the need of alternative methods. The European Centre for the Validation of Alternative Methods (ECVAM) is supporting alternative methods and validated the mouse embryonic stem cell test (mEST) as an appropriate test for developmental toxicity testing . The mEST is based on a permanent cell line of mouse embryonic stem cells that are differentiated into cardiomyocytes. The quantity of beating cardiomyocytes is the respective readout . The extrapolation from mouse to human is discussed controversially . Therefore, we establish a human embryonic stem cell test (hEST). As the usage of human embryos has ethical concerns, we use human induced pluripotent stem cells (hiPSC). These cells originate from fibroblasts which were reprogrammed into stem cells that cover all the characteristics of embryonic stem cells like self-renewal and pluripotency . To establish a hEST, hiPSC are differentiated into cardiomyocytes with the aim of evaluating more endpoints than the mEST. Therefore, we already established the differentiation of hiPSC to cardiomyocytes, achieving beating cardiomyocytes evenly in the entire dish which is a basic requirement for recording the electrical activity on microelectrode arrays (MEA). As the differentiation protocol represents the embryonic development of cardiomyocytes, the day of the first electrical signal could be a specific functional endpoint to measure. Furthermore, the number of electrodes recording a signal over time could be evaluated as another endpoint indicating maturation of the cells. When the differentiation of hiPSC to cardiomyocytes is established on MEAs, it is possible to screen substances for their toxic potential on the electrical activity of cardiomyocytes and therefore on the entire human cardiac system. References 1 Test No. 414 Prenatal Development Toxicity Study: TG414 (OECD Publishing, 2001). 2 Test No. 426 Developmental Neurotoxicity Study: TG426 (OECD Publishing, 2007). 3 A. E. M. Seiler and H. Spielmann, ‘The validated embryonic stem cell test to predict embryotoxicity in vitro’, Nature protocols 6 (2011), 961–78. 4 H.-y. Lee, A. L. Inselman, J. Kanungo and D. K. Hansen, ‘Alternative models in developmental toxicology’, Systems biology in reproductive medicine 58 (2012), 10–22. 5 J. Bailey, M. Thew and M. Balls, ‘Predicting human drug toxicity and safety via animal tests: Can any one species predict drug toxicity in any other, and do monkeys help?’, Alternatives to laboratory animals : ATLA 43 (2015), 393–403. 6 K. Takahashi, K. Tanabe, M. Ohnuki, M. Narita, T. Ichisaka, K. Tomoda and S. Yamanaka, ‘Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors’, Cell 131 (2007), 861–72. Keywords: hiPSC, cardiomyocytes, MEA, embryonic, development 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: Wuttke S, Brockerhoff G, Nimtz L, Tigges J and Fritsche E (2019). Electrical activity of developing cardiomyocytes. Conference Abstract: MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays. doi: 10.3389/conf.fncel.2018.38.00012 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: 17 Mar 2018; Published Online: 17 Jan 2019. * Correspondence: Ms. Saskia Wuttke, Leibniz-Institut für umweltmedizinische Forschung (IUF), Modern Risk Assessment and Sphere Biology, Dusseldorf, NRW, 40225, Germany, saskia.wuttke@iuf-duesseldorf.de 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 Saskia Wuttke Gabriele Brockerhoff Laura Nimtz Julia Tigges Ellen Fritsche Google Saskia Wuttke Gabriele Brockerhoff Laura Nimtz Julia Tigges Ellen Fritsche Google Scholar Saskia Wuttke Gabriele Brockerhoff Laura Nimtz Julia Tigges Ellen Fritsche PubMed Saskia Wuttke Gabriele Brockerhoff Laura Nimtz Julia Tigges Ellen Fritsche 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.