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Development of a toxicological assay for prediction of drug-induced seizure in human iPS cell-derived neurons

Research Project

Project/Area Number 17K15577
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General pharmacology
Research InstitutionTohoku University

Principal Investigator

Odawara Aoi  東北大学, 材料科学高等研究所, JSPS特別研究員(PD) (80795287)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsヒトiPS細胞由来ニューロン / 平面微小電極アレイ / 同期バースト発火 / 薬効評価 / 人工知能 / AI
Outline of Final Research Achievements

Functional evaluation assays using human induced pluripotent stem cell (hiPSC)-derived neurons are expected to predict the convulsion toxicity of new drugs. However, culture protocol on the micro-electrode array (MEA) in hiPSC-derived neurons and an evaluation index of MEA data are not well known. In this study, we investigated the difference of spontaneous firings and drug responses depending on the type of human iPS cell-derived neurons, cell density, medium conditions, and astrocyte co-culture conditions. It was found that the responsiveness differs depending on the culture conditions, and that one parameter is difficult to detect seizure-like toxicity. We also show that the synchronized burst firings (SBFs) detection method using AI, nonlinear time series analysis method, and frequency analysis method are effective as analysis method.

Academic Significance and Societal Importance of the Research Achievements

ヒトiPS細胞由来ニューロンの微小電極アレイ(MEA)計測法を用いた薬剤性痙攣予測法は、国内外で製薬会社も含めた取り組みが行われており、本研究成果は、実用化を推進する成果であり、社会的意義は大きい。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (19 results)

All 2019 2018 2017

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (16 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Toxicological evaluation of convulsant and anticonvulsant drugs in human induced pluripotent stem cell-derived cortical neuronal networks using an MEA system2018

    • Author(s)
      Odawara A.、Matsuda N.、Ishibashi Y.、Yokoi R.、Suzuki I.
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 10416-10416

    • DOI

      10.1038/s41598-018-28835-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Temporally coordinated spiking activity of human induced pluripotent stem cell-derived neurons co-cultured with astrocytes2018

    • Author(s)
      Kayama Tasuku、Suzuki Ikuro、Odawara Aoi、Sasaki Takuya、Ikegaya Yuji
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 495 Issue: 1 Pages: 1028-1033

    • DOI

      10.1016/j.bbrc.2017.11.115

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of synchronized burst firing in cultured human induced pluripotent stem cell-derived neurons using a 4-step method2018

    • Author(s)
      Matsuda N.、Odawara A.、Katoh H.、Okuyama N.、Yokoi R.、Suzuki I.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 497 Issue: 2 Pages: 612-618

    • DOI

      10.1016/j.bbrc.2018.02.117

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Nano-fiber deviceを用いたヒトiPS細胞由来ニューロンのMEA計測2019

    • Author(s)
      小田原あおい, 堀晃輔, 遠井紀江, 饗庭一博, 鈴木郁郎
    • Organizer
      日本安全性薬理研究会 第10回学術年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Assessment of seizure liability in human iPSC-derived neurons using AI2019

    • Author(s)
      松田 直毅, 小田原あおい, 鈴木郁郎
    • Organizer
      第92回 日本薬理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒトiPS細胞由来神経ネットワークを用いた痙攣毒性のAI予測2019

    • Author(s)
      松田 直毅, 小田原あおい, 鈴木郁郎
    • Organizer
      第18回 日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Toxicological evaluation of conversant and anticonvulsant drugs in human induced pluripotent stem cell derived cortical neuronal networks using an MEA system2018

    • Author(s)
      Aoi Odawara, Naoki Matsuda, Ikuro Suzuki
    • Organizer
      ISSCR 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MEAシステムを用いたヒトiPS細胞由来末梢ニューロンの痛み応答評価2018

    • Author(s)
      小田原あおい, 松田直毅, 鈴木郁郎
    • Organizer
      第45回 日本毒性学会学術年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] MEAシステムを用いたヒトiPS細胞由来感覚ニューロンの痛み応答評価2018

    • Author(s)
      小田原あおい, 松田直毅, 鈴木郁郎
    • Organizer
      日本安全性薬理研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒトiPS細胞由来末梢ニューロンを用いた痛み応答評価2018

    • Author(s)
      小田原あおい, 松田直毅, 鈴木郁郎
    • Organizer
      再生医療学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Electrophysiological Pain Responses in Cultured Human iPSC-Derived Sensory Neurons Using High-Throughput Multi-Electrode Array System2018

    • Author(s)
      Aoi Odawara, Naoki Matsuda, Yuto Ishibashi, Ikuro Suzuki
    • Organizer
      Society of toxicology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] MEAシステムを用いたヒトiPS細胞由来感覚ニューロンのin vitro痛み応答計測2017

    • Author(s)
      小田原あおい, 飯田拓也, 松田直毅, 鈴木郁郎
    • Organizer
      生体医工学会
    • Related Report
      2017 Research-status Report
  • [Presentation] MEAシステムを用いたヒトiPS細胞由来末梢ニューロンの痛み応答評価2017

    • Author(s)
      小田原あおい, 松田直毅, 鈴木郁郎
    • Organizer
      日本毒性学会
    • Related Report
      2017 Research-status Report
  • [Presentation] MEAを用いたヒトiPS細胞由来末梢ニューロンの痛み評価2017

    • Author(s)
      小田原あおい, 松田直毅, 鈴木郁郎
    • Organizer
      電気学会・電子・情報システム部門大会
    • Related Report
      2017 Research-status Report
  • [Presentation] ヒトiPSC由来末梢ニューロンを用いた抗癌剤の痛み応答評価2017

    • Author(s)
      小田原あおい, 松田直毅, 鈴木郁郎
    • Organizer
      ライフサポート学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] MEA システムを用いたヒト iPS 細胞由来末梢ニューロンの痛み応答評価2017

    • Author(s)
      小田原あおい, 松田直毅, 鈴木郁郎
    • Organizer
      日本動物実験代替法学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Pain responses in human iPSC-derived sensory neurons using MEA system2017

    • Author(s)
      Aoi Odawara, Takuya Iida, Naoki Matsuda1 Ryan Arant, Ikuro Suzuki
    • Organizer
      International Society for Stem Cell Research
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Pain responses of cultured human iPSC-derived sensory neurons using high-throughput MEA system2017

    • Author(s)
      Aoi Odawara, Naoki Matsuda, Yuto Ishibashi, Ikuro Suzuki
    • Organizer
      Safety pharmacology society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Induction of epileptiform activity and effects of anti-epilepsy drugs in cultured human induced pluripotent stem cell-derived cortical neuronal networks2017

    • Author(s)
      Aoi Odawara, Naoki Matsuda, Ikuro Suzuki
    • Organizer
      American Epilepsy Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2020-03-30  

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