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
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1
IUF-Leibniz Research Institute for Environmental Medicine, Germany
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2
IUF-Leibniz Research Institute for Environmental Medicine, Germany
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3
Université de Strasbourg, Institut de Génétique et de Biologie Moléculaire et Cellulaire, France
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4
Heinrich-Heine-Universität, Institute of Clinical Neuroscience and Medical Psychology, Germany
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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
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Received:
22 Jun 2016;
Published Online:
24 Jun 2016.
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Correspondence:
Dr. Laura Nimtz, IUF-Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany, Laura.Nimtz@IUF-duesseldorf.de