MEA technology combined with person-specific human iPSC-based cortical circuits for drug sensitivity and tolerance testing.
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1
University of Gothenburg, Sweden
Human induced pluripotent stem cell (hiPSC) technology provides the opportunity for new identified drug candidate evaluation in person-specific CNS disease model systems with the specific aim to achieve personalized medicine. Person specific drug tolerance testing, i. e. risk evaluation for the occurrence of harmful side effects of prescribed neuropharmaka, represent an unaddressed opportunity to apply person-specific hiPSC-based CNS-disease model systems.
A major milestone for this translational medical approach might be functional human neuronal model systems solely achieved by using person-derived cells, and thus, exclude allogenic or xenogenic co-culture approaches. Highly functional neuronal assemblies comprise of electrophysiological active and functional interconnected neurons that are capable to generate bursting activity that spread over the entire neuronal circuit, i. e. population-wide bursting activity. Microelectrode array (MEA) technology applied on hiPSC-derived neurons allows to study population-wide bursting of human neurons. Thus, combing MEA-chips with human person-specific hiPSCs neural cells might represents a valuable approach to understand drug-induced side effects of prescribed neuropharmaka on human neuronal network level.
I will present our approach for the reproducible generation of PB-generating human cortical circuits on MEAs solely using person-specific hiPSC-derived neural cells without co-culturing of rat or human astrocytes. We applied this approach to show how a mood-balancing and a anti-seizure drug influencing human cortical activity at network level. The transition of cortical network function of human neurons exposed to therapeutical effective and intoxication concentration of prescribed neuropharmaka reflect described in vivo brain activity pattern. We successful counteract the drug-induced pathophysiological network function.
The presented approach paves the way for person-specific neuropharmacological drug-evaluation and CNS disease modelling.
Acknowledgements
The author would like to acknowledge grants from the Åhlén Foundation, the Fredrik and Ingrid Thuring Foundation, the Psychiatry Research Foundation in Gothenburg, Åke Wiberg Foundation and Alzheimerfonden.
Keywords:
IPSC-derived neurons,
neuronal networks,
Lithium,
drug tests,
Epilepsy,
mood stabilizers,
antiepileptic drug,
microelectrode array
Conference:
MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays, Reutlingen, Germany, 4 Jul - 6 Jul, 2018.
Presentation Type:
Oral Presentation
Topic:
Stem cell-derived applications
Citation:
Illes
S
(2019). MEA technology combined with person-specific human iPSC-based cortical circuits for drug sensitivity and tolerance testing..
Conference Abstract:
MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays.
doi: 10.3389/conf.fncel.2018.38.00002
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Received:
01 Feb 2018;
Published Online:
17 Jan 2019.
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Correspondence:
Dr. Sebastian Illes, University of Gothenburg, Gothenburg, Sweden, sebastian.illes@neuro.gu.se