MEA

# 豊富な経験に基づいたMEAアッセイの技術を有します。

2014年にHuman iPSC-derived neuronのMEA計測を初めて報告してから、100種類以上のiPS由来ニューロン(中枢、末梢)のMEA計測を実施し、培養法の最適化から得られたデータの解析法を開発してきました。疾患iPS細胞由来ニューロンを含めて、医薬品をはじめとする化合物の安全性評価、薬効薬理試験の多数の経験を有します。Vivoを外挿する毒性予測やMoA予測を実施します。また、急性脳スライスのMEA試験(LTP試験含む)やヒトiPS心筋のMEA試験技術を有しています。

参考論文(抜粋)
Central Nervus System(CNS)

Y. Ishibashi, N Nagafuku, K Kinoshita, A Okamura, T shirakawa, I Suzuki*,  Verification in seizure liability of compounds based on comparison between in vitro functional activity in cultured neurons and in vivo cerebrospinal fluid concentration for approaching in vitro to in vivo extrapolation, Toxicology and Applied pharmacology. 476;116675, 2023 DOI

Y. Ishibashi, N. Nagafuku, Y. Kanda, I. Suzuki1 * Evaluation of neurotoxicity for pesticide-related compounds in human iPS cell-derived neurons 2 using microelectrode array. Toxicology in vitro. 93;105668, 2023 DOI

I. Suzuki*, N. Matsuda, X. Han, S. Noji, M. Shibata, N. Nagafuku, Y. Ishibashi, Large-area field potential imaging having single neuron resolution using 236,880 electrodes CMOS-MEA technology, Advanced Science, 2023, 1-23 DOI

X Han, N Matsuda, Y Ishibashi, A Odawara; S Takahashi; N Tooi, K Kinoshita, I Suzuki*, “A functional neuron maturation device provides convenient application on microelectrode array for neural network measurement” Biomaterials Research, 26, 84, 1-17,2022 DOI

N Matsuda, A Odawara, Y Ishibashi, K Kinoshita, A Okamura, T Shirakawa, I Suzuki*. Raster plots machine learning to predict the seizure liability of drugs and to identify drugs. Sci Rep. 2022 12(1):2281. DOI

Y. Ishibashi, S. Kimura, I Suzuki*,  Responses to antibiotics in human iPSC-derived neurons based on the clinical antibiotic associated encephalopathy classification, 2022, 47(10), p429-437. The Journal of Toxicological Sciences. DOI

R Yokoi, T Kuroda, N Matsuda, A Odawara, I Suzuki*. Electrophysiological responses to seizurogenic compounds dependent on E/I balance in human iPSC-derived cortical neuronal networks. Journal of Pharmacological Sciences. 2022 148(2):267-278. DOI

Shirakawa T, Suzuki I*. “Approach to Neurotoxicity using Human iPSC Neurons: Consortium for Safety Assessment using Human iPS Cells”. Current Pharmaceutical Biotechnology. 2019 21(9):780-786, DOI

Yokoi R, Okabe N, Matsuda N, Odawara A, Karashima A, Suzuki I*. “Impact of sleep-wake-associated neuromodulators and repetitive low-frequency stimulation on human iPSC-derived neurons.” Frontiers in Neuroscience. 2019 May, 13:554,1-15, DOI

Odawara, A., Matsuda N., Ishibashi Y., Yokoi R., and Suzuki, I.* “Toxicological evaluation of convulsant and anticonvulsant drugs in human induced pluripotent stem cell-derived cortical neuronal networks using an MEA system” Scientific Reports, 8(1), 10416(2018)DOI

Matsuda N, Odawara A, Katoh H, Okuyama N, Yokoi R, Suzuki, I.* Detection of synchronized burst firing in cultured human induced pluripotent stem cell-derived neurons using a 4-step method. Biochem Biophys Res Commun. 2018, 497, 612-618.DOI

Odawara, A., Katoh, H., Matsuda N., and Suzuki, I.* “Physiological maturation and drug responses of human induced pluripotent stem cell-derived cortical neuronal networks in long-term culture” Scientific Reports, 6, 26181(2016)DOI

Odawara, A., Katoh, H., Matsuda N., and Suzuki, I.* “Induction of long-term potentiation and depression phenomena in human induced pluripotent stem cell-derived cortical neurons.” Biochem Biophys Res Commun. (2016)469(4):856-62. DOI

Odawara, A., Gotoh, M., and Suzuki, I.* “Long-term electrophysiological activity and pharmacological response in human induced pluripotent stem cell derived neuron and astrocyte co-culture” Biochem Biophys Res Commun. (2014)443(4):1176-81.DOI

Sensory neurons

X. Han, N. Matsuda, Y. Ishibashi, M. Shibata, I Suzuki*, An In Vitro Assessment Method for Chemotherapy-Induced Peripheral Neurotoxicity Caused by Anti-Cancer Drugs Based on Electrical Measurement of Impedance Value and Spontaneous Activity, Pharmaceutics, 15(12), 2788, 2023 DOI

I. Suzuki*, N. Matsuda, X. Han, S. Noji, M. Shibata, N. Nagafuku, Y. Ishibashi, Large-area field potential imaging having single neuron resolution using 236,880 electrodes CMOS-MEA technology, Advanced Science, 2023, 1-23 DOI

A Odawara, M Shibata, Y Ishibashi, N Nagafukum N matsuda, I Suzuki* In Vitro Pain Assay Using Human iPSC-Derived Sensory Neurons and Microelectrode Array. Toxicological Sciences. 2022 188(1):131-141. DOI

アストロサイトのMEA計測、脳オルガノイドのMEA計測技術および得られたデータの低周波成分解析技術を有し、化合物評価を行っています。

画像9.png

 

参考論文
Astrosyte

T. Kuroda, N. Matsuda, Y. Ishibashi, I Suzuki*,  Assessment of astrocytic electrophysiological responses to seizurogenic compounds using planner microelectrode array, Frontiers in Neuroscience. 16:1050150, 2022, DOI

Brain Organoids

R. Yokoi, N Nagafuku, Y. Ishibashi, N. Matsuda, I Suzuki*,  Contraindicated Drug Responses in Dravet Syndrome Brain Organoids Utilizing Micro Electrode Array Assessment Methods, Organoids 2(4) 177-191, 2023 DOI

I. Suzuki*, N. Matsuda, X. Han, S. Noji, M. Shibata, N. Nagafuku, Y. Ishibashi, Large-area field potential imaging having single neuron resolution using 236,880 electrodes CMOS-MEA technology, Advanced Science, 2023, 1-23 DOI

Yokoi R, Shibata M, Odawara A, Ishibashi Y, Nagafuku N, Matsuda N, Suzuki I*. Analysis of signal components < 500 Hz in brain organoids coupled to microelectrode arrays: a reliable test- bed for preclinical seizure liability assessment of drugs and screening of antiepileptic drugs. Biochem and Biophys Res. 2021 28:101148. DOI

 

同一サンプルにおけるインピーダンス、細胞外電位、細胞形態の複数アッセイを実施し、化合物応答を多面的に解析しています。

画像8.png

 

参考論文
Impedance

X. Han, N. Matsuda, Y. Ishibashi, M. Shibata, I Suzuki*, An In Vitro Assessment Method for Chemotherapy-Induced Peripheral Neurotoxicity Caused by Anti-Cancer Drugs Based on Electrical Measurement of Impedance Value and Spontaneous Activity, Pharmaceutics, 15(12), 2788, 2023 DOI