Seizure Liability Assessment in Human IPS Neurons using Microelectrode Array and HTS via Calcium-flux
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1
Ncardia (Germany), Germany
New, higher throughput predictive models are always required to address the evolving needs of preclinical R&D and safety assessment. Human neurons derived from induced pluripotent stem cells present a predictive, flexible and potent tool due to their unlimited availability, physiological relevance and lack of interspecies translatability issues. iPS-derived neurons express a plethora of neurotransmitters at physiologically-relevant levels. This can help to accelerate the assessment of clinically relevant issues such as psychological disorders, drug-induced seizure liability, peripheral neuropathy, and other CNS-related issues. Here we present two models that take advantage of instrumentation featuring 96 (or 384) well plates with automated compound handling/robotics and measurements for a cost-effective and animal-free neurological phenotypic assessment. 1. 96/384 well optical readout: calcium transient flux induced by neurotransmitters using the Hamamatsu µCell. Here we show that multiple monoamine neurotransmitters, glutamate, NMDA, acetlycholine, etc. induce increases a fluorescent calcium reporter in a concentration-dependent manner.
2. 96 well electrical (extracellular field potential) recordings: three separate neuronal populations were co-cultured with isogenic iPS astrocytes until mature, synchronous burst firing was achieved. The effects of 9 seizure-related compounds (as part of the HESI Neutox MEA consortium) on the neuronal activity using the Axion Maestro MEA technology were assessed and results were correlated to established primary rodent models.
Keywords:
Seizures,
stem cell derived neurons,
CNS.4U,
Seizure liability,
Central Nervous System
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:
Hess
D,
Kettenhofen
R and
Luerman
G
(2019). Seizure Liability Assessment in Human IPS Neurons using Microelectrode Array and HTS via Calcium-flux.
Conference Abstract:
MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays.
doi: 10.3389/conf.fncel.2018.38.00004
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Received:
15 Mar 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Dr. Dietmar Hess, Ncardia (Germany), Cologne, Germany, dietmar.hess@ncardia.com