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Synaptic Connectors and AI-Based Analytical Systems for Super-Recovery of Injured Neural Function and Sensory Perception

Research Project

Project/Area Number 22K19590
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionAichi Medical University

Principal Investigator

Takeuchi Kosei  愛知医科大学, 医学部, 教授 (90206946)

Co-Investigator(Kenkyū-buntansha) 柳原 大  東京大学, 大学院総合文化研究科, 教授 (90252725)
瀬尾 憲司  新潟大学, 医歯学系, 教授 (40242440)
Project Period (FY) 2022-06-30 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2024: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2023: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2022: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords再生医療 / 脊髄損傷 / リハビリテーション / 神経再生 / AI定量解析 / リハビリテーションモデル / 神経回路 / 神経再生治療 / シナプス / 細胞外環境
Outline of Research at the Start

中枢神経・脊髄損傷の治療応用において、モデル動物脊髄損傷での運動機能評価や痛み評価を正確に定量化しヒト運動機能改善に外挿できる系として、我々はAI機械学習から詳細な機能回復パラメータを抽出しヒトの機能改善に外挿可能な解析系を目標とする。特に、我々は人工シナプスコネクターの合成に成功、モデル動物の急速な生理機能回復を報告した (Science 2020)。また、神経再生の阻害因子であるコンドロイチン硫酸の発現抑制が、劇的回復を示すことを報告し(Nature Commun.2014)創薬展開に繋げている。本研究では従来とは全く異なる2つのこの新しいコンセプトを融合した超回復系を駆使し、上記の課題に挑む。

Outline of Final Research Achievements

Although numerous basic studies have aimed to promote functional recovery after spinal cord injury, few systems allow for reliable extrapolation of recovery outcomes to humans. We have reported that the use of synthetic-synaptic connectors, combined with suppression of chondroitin sulfate leads to rapid physiological recovery in animal models and enables potential therapeutic applications. Utilizing these highly effective recovery systems, we integrated AI-based machine learning with the development of analytical devices to quantitatively evaluate motor function in SCI models and, notably, to accurately assess pain, an area previously lacking detailed analysis. This approach enabled us to establish a platform that bridges model animal data with human motor function recovery. By extracting detailed functional recovery parameters, we successfully presented an analytical framework that allows translational application to human rehabilitation and drug discovery.

Academic Significance and Societal Importance of the Research Achievements

本研究は、脊髄損傷による深刻な運動障害や痛みに対し、回復困難とされてきた現状を打破する革新的アプローチとなる。とくに人工シナプスコネクターと抑制因子制御による神経回復に加え、AI解析を融合することで、動物実験からヒトへの外挿性を飛躍的に高めることに成功した。再生医療や創薬、リハビリ評価の次世代標準となる可能性を秘めており、超高齢社会におけるQOL改善と医療負担軽減に貢献する社会的意義は極めて大きいと言える。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (17 results)

All 2025 2024 2023 2022 Other

All Int'l Joint Research (3 results) Journal Article (9 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 9 results,  Open Access: 9 results) Presentation (2 results) Remarks (3 results)

  • [Int'l Joint Research] Oxford University/Cambridge MRC Center(英国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] DZNE(ドイツ)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] Miami University(米国)

    • Related Report
      2022 Research-status Report
  • [Journal Article] Creating Alternative Afferent Input to Facilitate the Regeneration of Injured Primary Afferent Neurons2025

    • Author(s)
      Sawada Emi、Yamamoto Toru、Kishimoto Naotaka、Ooishi Dai、Sasakura Hiroyuki、Takeuchi Kosei、Seo Kenji
    • Journal Title

      Cureus

      Volume: 14(1) Pages: 4813-4813

    • DOI

      10.7759/cureus.78708

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endogenous chondroitin extends the lifespan and healthspan in C. elegans.2024

    • Author(s)
      Shibata Y, Tanaka Y, Sasakura H, Morioka Y, Sassa T, Fujii S, Mitsuzumi K, Ikeno M, Kubota Y, Kimura K, Toyoda H, Takeuchi K, Nishiwaki K.
    • Journal Title

      Sci Rep.

      Volume: 14 Issue: 1 Pages: 4813-4813

    • DOI

      10.1038/s41598-024-55417-7

    • Related Report
      2024 Annual Research Report 2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Human-induced pluripotent stem cell-derived neural stem/progenitor cell ex vivo gene therapy with synaptic organizer CPTX for spinal cord injury2024

    • Author(s)
      Saijo Y, Nagoshi N, Kawai M, Kitagawa T, Suematsu Y, Ozaki M, Shinozaki M, Kohyama J, Shibata S, Takeuchi K, Nakamura M, Yuzaki M, Okano H.
    • Journal Title

      Stem Cell Reports.

      Volume: 19 Issue: 3 Pages: 100393-100393

    • DOI

      10.1016/j.stemcr.2024.01.007

    • Related Report
      2024 Annual Research Report 2023 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inhibitory effects of estetrol on the invasion and migration of immortalized human endometrial stromal cells2024

    • Author(s)
      Wakatsuki A, Lin Y, Kojima S, Matsushita H, Takeuchi K, Umezawa K.
    • Journal Title

      Endocrine Journal

      Volume: 71 Issue: 2 Pages: 199-206

    • DOI

      10.1507/endocrj.EJ23-0397

    • ISSN
      0918-8959, 1348-4540
    • Related Report
      2024 Annual Research Report 2023 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endogenous chondroitin extends lifespan by inhibiting VHA-7-mediated tubular lysosome formation2024

    • Author(s)
      Shibata Yukimasa、Tanaka Yuri、Mori Shunsuke、Mitsuzumi Kaito、Fujii Shion、Sasakura Hiroyuki、Morioka Yuki、Sugioka Kenji、Takeuchi Kosei、Nishiwaki Kiyoji
    • Journal Title

      Scientific Reports

      Volume: 14 Issue: 1 Pages: 29651-29651

    • DOI

      10.1038/s41598-024-80242-3

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inhibition of Transglutaminase 2 Reduces Peritoneal Injury in a Chlorhexidine-Induced Peritoneal Fibrosis Model2023

    • Author(s)
      Kunoki S, Tatsukawa H, Sakai Y, Kinashi H, Kariya T, Suzuki Y, Mizuno M, Yamaguchi M, Sasakura H, Ikeno M, Takeuchi K, Ishimoto T, Hitomi K, Ito Y
    • Journal Title

      Laboratory Investigation

      Volume: 103 Issue: 4 Pages: 100050-100050

    • DOI

      10.1016/j.labinv.2022.100050

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased urinary albumin leakage is related to injuries of glomerular glycocalyx and podocytes, and associated with tubular dysfunction in preeclampsia.2023

    • Author(s)
      Watanabe K, Okamoto T, Saitou T, Iwasaki A, Matsushita H, Takeuchi K, Asai A, Ito Y, Hara M, Wakatsuki A.
    • Journal Title

      Pregnancy Hypertens

      Volume: 17 Pages: 1-17

    • DOI

      10.1016/j.preghy.2023.02.001

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 2. Highly selective transgene expression through the flip-excision switch system by using a unilateral spacer sequence.2023

    • Author(s)
      Matsushita, N.*, Kato, S.*, Nishizawa, K., Sugawara, M., Takeuchi, K., Miyasaka, Y., Mashimo, T. and Kobayashi, K. * Equal contribution
    • Journal Title

      Cell Rep. Methods

      Volume: 3 Issue: 2 Pages: 100393-100393

    • DOI

      10.1016/j.crmeth.2022.100393

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 3. Catecholaminergic cell type-specific expression of Cre recombinase in knock-in transgenic rats generated by the Combi-CRISPR technology.2022

    • Author(s)
      Matsushita, N., Nishizawa, K., Kato, S., Iguchi, Y., Fukabori, R., Takeuchi, K., Miyasaka, Y., Mashimo, T. and Kobayashi, K.
    • Journal Title

      J. Neurosci. Methods

      Volume: 381 Pages: 109707-109707

    • DOI

      10.1016/j.jneumeth.2022.109707

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 人為的シナプスコネクトと神経再生環境場整備による後期脊髄損傷からの回復2022

    • Author(s)
      笹倉 寛之、鈴木 邦道、池野 正史、森岡 幸、武内 由佳、柚崎 通介、武内 恒成
    • Organizer
      Neuro2022
    • Related Report
      2022 Research-status Report
  • [Presentation] 遺伝子の機能と神経疾患に対する細胞治療への応用2022

    • Author(s)
      池野 正史、笹倉 寛之、武内 恒成1
    • Organizer
      Neuro2022
    • Related Report
      2022 Research-status Report
  • [Remarks] https://www.take-lab.org/

    • Related Report
      2024 Annual Research Report
  • [Remarks] 教室ホームページ

    • URL

      https://www.take-lab.org/

    • Related Report
      2023 Research-status Report
  • [Remarks] https://www.take-lab.org/

    • Related Report
      2022 Research-status Report

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Published: 2022-07-05   Modified: 2026-01-16  

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