Establishment of a Human Neuronal Network Assessment System by Using a Human Neuron/Astrocyte Co-Culture Derived from Fetal Neural Stem/Progenitor Cells.
Using human cell models mimicking the central nervous system (CNS) provides a better understanding of the human CNS, and it is a key strategy to improve success rates in CNS drug development. In the CNS, neurons function as networks in which astrocytes play important roles. Thus, an assessment system of neuronal network functions in a co-culture of human neurons and astrocytes has potential to accelerate CNS drug development. We previously demonstrated that human hippocampus-derived neural stem/progenitor cells (HIP-009 cells) were a novel tool to obtain human neurons and astrocytes in the same culture. In this study, we applied HIP-009 cells to a multielectrode array (MEA) system to detect neuronal signals as neuronal network functions. We observed spontaneous firings of HIP-009 neurons, and validated functional formation of neuronal networks pharmacologically. By using this assay system, we investigated effects of several reference compounds, including agonists and antagonists of glutamate and γ-aminobutyric acid receptors, and sodium, potassium, and calcium channels, on neuronal network functions using firing and burst numbers, and synchrony as readouts. These results indicate that the HIP-009/MEA assay system is applicable to the pharmacological assessment of drug candidates affecting synaptic functions for CNS drug development.
Next Generation Systems CFU, Eisai Product Creation Systems, Eisai Co., Ltd., Tokodai, Tsukuba, Ibaraki, Japan k7-fukushima@hhc.eisai.co.jp.
Kazuyuki
K
Fukushima
Next Generation Systems CFU, Eisai Product Creation Systems, Eisai Co., Ltd., Tokodai, Tsukuba, Ibaraki, Japan.
Yuji
Y
Miura
Biopharmaceutical Assessment CFU, Eisai Product Creation Systems, Eisai Co., Ltd., Tokodai, Tsukuba, Ibaraki, Japan.
Kohei
K
Sawada
Next Generation Systems CFU, Eisai Product Creation Systems, Eisai Co., Ltd., Tokodai, Tsukuba, Ibaraki, Japan.
Kazuto
K
Yamazaki
Next Generation Systems CFU, Eisai Product Creation Systems, Eisai Co., Ltd., Tokodai, Tsukuba, Ibaraki, Japan.
Masashi
M
Ito
D000200:Action Potentials / Q000502:physiology; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002490:Central Nervous System / Q000378:metabolism / Q000502:physiology; D018920:Coculture Techniques / Q000379:methods; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008839:Microelectrodes; D009415:Nerve Net / Q000166:cytology* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005680:gamma-Aminobutyric Acid
human neuron/astrocyte co-culture; multielectrode array; neural stem/progenitor cells; neuronal networks