title: Long-term electrophysiological activity and pharmacological response of a human induced pluripotent stem cell-derived neuron and astrocyte co-culture.
abstract: Human induced pluripotent stem cell (hiPSC)-derived neurons may be effectively used for drug discovery and cell-based therapy. However, the immaturity of cultured human iPSC-derived neurons and the lack of established functional evaluation methods are problematic. We here used a multi-electrode array (MEA) system to investigate the effects of the co-culture of rat astrocytes with hiPSC-derived neurons on the long-term culture, spontaneous firing activity, and drug responsiveness effects. The co-culture facilitated the long-term culture of hiPSC-derived neurons for >3 months and long-term spontaneous firing activity was also observed. After >3 months of culture, we observed synchronous burst firing activity due to synapse transmission within neuronal networks. Compared with rat neurons, hiPSC-derived neurons required longer time to mature functionally. Furthermore, addition of the synapse antagonists bicuculline and 6-cyano-7-nitroquinoxaline-2,3-dione induced significant changes in the firing rate. In conclusion, we used a MEA system to demonstrate that the co-culture of hiPSC-derived neurons with rat astrocytes is an effective method for studying the function of human neuronal cells, which could be used for drug screening.
authors.affiliation: Graduate School of Bionics, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo 192-0982, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Odawara
authors.affiliation: School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo 192-0982, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Saitoh
authors.affiliation: Graduate School of Bionics, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo 192-0982, Japan.
authors.forename: A H
authors.initials: AH
authors.lastname: Alhebshi
authors.affiliation: Graduate School of Bionics, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo 192-0982, Japan; School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo 192-0982, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Gotoh
authors.affiliation: Graduate School of Bionics, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo 192-0982, Japan; School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji, Tokyo 192-0982, Japan. Electronic address: isuzuki@stf.teu.ac.jp.
authors.forename: I
authors.initials: I
authors.lastname: Suzuki
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D001640:Bicuculline / Q000494:pharmacology; D002454:Cell Differentiation; D018920:Coculture Techniques; D004353:Drug Evaluation, Preclinical; D055724:Electrophysiological Phenomena; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D009415:Nerve Net / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D051381:Rats; D009435:Synaptic Transmission
chemical_list: D018377:Neurotransmitter Agents; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001640:Bicuculline
keywords: Astrocyte co-culture; Human induced pluripotent stem cell-derived neurons; Long-term measurement; Multi-electrode array; Pharmacological effects