Establishment Of Electrically Active Neuronal Networks From Human Induced Pluripotent Stem Cell-Derived Neurospheres As An Alternative In Vitro Method To Study Neurotoxic Effects On Multielectrode Arrays

Abstract

Event Abstract Back to Event Establishment Of Electrically Active Neuronal Networks From Human Induced Pluripotent Stem Cell-Derived Neurospheres As An Alternative In Vitro Method To Study Neurotoxic Effects On Multielectrode Arrays Laura Nimtz1*, Maxi Hofrichter2, Yaschar Kabiri2, Jean-Marc Egly3, Stephan Theiss4, James Adjaye5 and Ellen Fritsche1 1 IUF-Leibniz Research Institute for Environmental Medicine, Germany 2 IUF-Leibniz Research Institute for Environmental Medicine, Germany 3 Université de Strasbourg, Institut de Génétique et de Biologie Moléculaire et Cellulaire, France 4 Heinrich-Heine-Universität, Institute of Clinical Neuroscience and Medical Psychology, Germany 5 Heinrich-Heine-Universität, Institut für Stammzellforschung und Regenerative Medizin, Germany Today neurotoxicity testing and drug development is highly resource-intensive. To predict adverse effects of various compounds to the central nervous system alternative approaches are required. These strategies should be affordable, sensitive, use mechanism-based methods which are also predictive for humans and allow medium-throughput screenings. Obtaining human material especially from neural tissue, however, is often not possible or bears ethical concerns. The electrical activity of in vitro generated neuronal networks is fundamental for the extrapolation of human in vitro data to the human in vivo situation. Therefore, we use human induced pluripotent stem cells (hiPSCs) to overcome these restrictions. We have established hiPSC-derived neural progenitor cells, cultured as 3D neurospheres, which are further differentiated into neuronal networks consisting of neurons and astrocytes. Using multielectrode arrays (MEA) we detected spontaneous electrophysiological activity from hiPSC-derived neuronal networks starting after two to three weeks of differentiation. Furthermore, our neuronal networks developed from single spikes to bursts indicating maturation over time. Treatment with tetrodotoxin resulted in a complete inhibition of the electrophysiological signals demonstrating that our hiPSC-derived neuronal networks are sodium-ion channel dependent. However, in contrast to neuronal networks derived from rat neurospheres, hiPSC-derived networks were less active and exhibited no network synchronicity within the cultivation time. Moreover, one of the main drawbacks of MEA recording is the high variability between the developing networks. This makes it highly important to optimize and standardize neuronal network development as well as the following measurement procedure. More data are needed to establish a screening-method for neurodevelopmental toxicity testing based on hiPSC-derived neuronal network activities. Conference: MEA Meeting 2016 | 10th International Meeting on Substrate-Integrated Electrode Arrays, Reutlingen, Germany, 28 Jun - 1 Jul, 2016. Presentation Type: Poster Presentation Topic: MEA Meeting 2016 Citation: Nimtz L, Hofrichter M, Kabiri Y, Egly J, Theiss S, Adjaye J and Fritsche E (2016). Establishment Of Electrically Active Neuronal Networks From Human Induced Pluripotent Stem Cell-Derived Neurospheres As An Alternative In Vitro Method To Study Neurotoxic Effects On Multielectrode Arrays. Front. Neurosci. Conference Abstract: MEA Meeting 2016 | 10th International Meeting on Substrate-Integrated Electrode Arrays. doi: 10.3389/conf.fnins.2016.93.00116 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: 22 Jun 2016; Published Online: 24 Jun 2016. * Correspondence: Dr. Laura Nimtz, IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany, Laura.Nimtz@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 Laura Nimtz Maxi Hofrichter Yaschar Kabiri Jean-Marc Egly Stephan Theiss James Adjaye Ellen Fritsche Google Laura Nimtz Maxi Hofrichter Yaschar Kabiri Jean-Marc Egly Stephan Theiss James Adjaye Ellen Fritsche Google Scholar Laura Nimtz Maxi Hofrichter Yaschar Kabiri Jean-Marc Egly Stephan Theiss James Adjaye Ellen Fritsche PubMed Laura Nimtz Maxi Hofrichter Yaschar Kabiri Jean-Marc Egly Stephan Theiss James Adjaye 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.