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Active control and simulator of neurons in regenerative transplantation treatment with the aid of environment control utilizing three-dimensional dynamic stimulations

Research Project

Project/Area Number 19H02089
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 20010:Mechanics and mechatronics-related
Research InstitutionYamagata University

Principal Investigator

Kosawada Tadashi  山形大学, 大学院理工学研究科, 教授 (10143083)

Co-Investigator(Kenkyū-buntansha) 馮 忠剛  山形大学, 大学院理工学研究科, 准教授 (10332545)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2021: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
KeywordsiPS細胞 / ニューロン分化・成長誘導制御 / 3次元ゲル包埋培養 / 3次元ニューロンネットワーク / in vitro移植シミュレータ / 超小型3次元振動ステージ / 3次元動的力学刺激環境 / 移植性促進法 / 3次元神経回路網 / iPS細胞由来ニューロン / ゲル包埋3D培養 / 3D動的力学刺激環境制御 / 3Dニューロンネットワーク構築制御 / 再生移植制御シミュレータ / iPS細胞の分化・成長誘導制御 / ニューロン簡易移植モデル / 分化・成長誘導制御
Outline of Research at the Start

生きている培養細胞に対し,3次元動的マイクロ力学刺激環境を自在に付加可能な超小型3次元振動ステージ・アクチュエータシステムを開発し,これにゲル包埋3次元培養法を組合せ,これまでとは全く異なる機械力学的原理に基づくiPS細胞から神経細胞への分化誘導,立体ニューロンネットワーク構築,さらにこれらを統合した3次元ニューロンのアクティブ再生移植制御・in vitro(培養ディシュ内)シミュレータの開発に挑戦する。
これにより,最近再生移植治療が開始されたパーキンソン病,および間もなく開始予定の脊髄損傷など重篤な神経系疾患への神経細胞再生移植治療を強力に支援する画期的システムへの展開を目指す。

Outline of Final Research Achievements

Not like a conventional approach but based on the principle of mechanics, a novel small sized piezoelectric 3-D vibration table is developed to impose dynamic stimulations on cultured living cells in order to support regenerative medicine. Together with scaffold utilizing gel-embedded 3-D culture, the device enables us to enforce 3-D micro dynamic stimulations upon the cultured neuronal networks. Appropriately soft but structurally stable scaffold is realized by optimization of collagen-gel concentration, which provides an effective method for the gel-embedded 3-D culture of neurons differentiated from iPS cells. Enforcing systematic 3-D dynamic stimulations upon gel-embedded neuronal networks by the developed 3-D vibration table, principle usefulness of the present study as a 3-D manipulation and active control method of neuronal networking as well as simulation system for regenerative transplantation medicine has been confirmed.

Academic Significance and Societal Importance of the Research Achievements

本研究では,iPS細胞を用いた再生治療に貢献するため,生きている培養細胞に対し従来の化学的誘導因子に加え,3次元の動的力学刺激を自在に付加し得る圧電駆動超小型3次元振動ステージを開発した。ゲル包埋3次元培養法と合わせ,これまでとは全く異なる力学的原理に基づく3次元ニューロンネットワークの創生・誘導制御および再生移植シミュレーションを可能とする革新的システムを開発した。今後の更なる研究により,脊髄損傷やパーキンソン病等神経系難病に対する再生移植治療の実現を支援・推進するデバイス,スキルに展開し得る可能性を提示した。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (17 results)

All 2022 2021 2020 2019 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] Physically-based structural modeling of a typical regenerative tissue analog bridges material macroscale continuum and cellular microscale discreteness and elucidates the hierarchical characteristics of cell-matrix interaction2022

    • Author(s)
      Zhonggang Feng, Kyohei Fujita, Mizuna Yano, Tadashi Kosawada, Daisuke Sato, Takao Nakamura, Mitsuo Umezu
    • Journal Title

      Journal of the Mechanical Behavior of Biomedical Materials

      Volume: 126 Pages: 1-17

    • DOI

      10.1016/j.jmbbm.2021.104956

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Novel In Vitro Simulator to Investigate Promotion of Reconstruction of Damaged Neuronal Cell Colony Differentiated from iPS Cells with the Aid of Micro Dynamic Stimulation2021

    • Author(s)
      Tadashi Kosawada, Taku Kitsunai, Zhonggang Feng, Kaoru Goto
    • Journal Title

      Technologies

      Volume: 9(4), 83 Issue: 4 Pages: 83-83

    • DOI

      10.3390/technologies9040083

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of docosahexaenoic acid or arachidonic acid supplementation on gene expression and contractile force of rat cardiomyocytes in primary culture2021

    • Author(s)
      MIZUNA YANO, YUTA UMEHARA, TOMOKAZU KUDO, TAKAO NAKAMURA, TADASHI KOSAWADA, ATSUYOSHI NISHINA, MASAKI SAZUKA, DAISUKE SATO, ZHONGGANG FENG
    • Journal Title

      BIOCELL

      Volume: 45(5) Pages: 12131229-12131229

    • Related Report
      2021 Annual Research Report
  • [Journal Article] 培養iPS細胞に対する動的力学刺激の影響と利用技術2020

    • Author(s)
      小沢田 正
    • Journal Title

      日本機械学会誌

      Volume: 123-1218 Pages: 18-21

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Fine control of endothelial VEGFR-2 activation: caveolae as fluid shear stress shelters for membrane receptors2019

    • Author(s)
      Shin, H, Haga, J.H., Kosawada, T., Kimura, K., Li, Y.S., Chien, S., Schmid-Schönbein, G.W.
    • Journal Title

      Biomechanics and Modeling in Mechanobiology

      Volume: 18 Issue: 1 Pages: 5-16

    • DOI

      10.1007/s10237-018-1063-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ヒト神経細胞の In vitro 3次元移植システムの動的力学刺激付加による影響評価2021

    • Author(s)
      石川 遼,小沢田正,馮忠剛,片岡駿
    • Organizer
      日本機械学会Dynamics and Design Conference 2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] 損傷ヒト神経細胞コロニーの再構築に及ぼす動的力学刺激の影響2021

    • Author(s)
      沼尻晃一,小沢田正,馮忠剛,大島友一
    • Organizer
      日本機械学会Dynamics and Design Conference 2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] Investigation on the Poisson's ratio of fibroblast-compacted collagen gels2020

    • Author(s)
      Feng Zhonggang, Kuramochi Shunya, Kosawada Tadashi, Sato Daisuke, Nakamura Takao, Umezu Mitsuo
    • Organizer
      生体医工学
    • Related Report
      2020 Annual Research Report
  • [Presentation] ヒト神経細胞のIn vitro 2次元移植システム構築及びそれに対する動的力学刺激の影響2020

    • Author(s)
      富澤圭悟,石原修平,小沢田正,馮忠剛
    • Organizer
      日本機械学会Dynamics and Design Conference 2020
    • Related Report
      2020 Annual Research Report
  • [Presentation] 3次元ゲル包埋神経細胞コロニー間におけるネットワーク形成に及ぼす動的力学刺激の影響2020

    • Author(s)
      片岡駿,金子哲也,小沢田正,馮忠剛
    • Organizer
      日本機械学会Dynamics and Design Conference 2020
    • Related Report
      2020 Annual Research Report
  • [Presentation] 損傷神経細胞コロニーの再構築に及ぼす動的力学刺激の影響2020

    • Author(s)
      大島友一,橘内琢,小沢田正,馮忠剛
    • Organizer
      日本機械学会Dynamics and Design Conference 2020
    • Related Report
      2020 Annual Research Report
  • [Presentation] 3次元ゲル包埋培養ヒト神経細胞の分化・成長に及ぼす動的力学刺激の影響2019

    • Author(s)
      小金澤 光,藤巻 匠,小沢田 正,馮 忠剛
    • Organizer
      LIFE2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒト神経細胞の二次元移植システム構築及びそれに対する動的力学刺激の影響2019

    • Author(s)
      石原修平,小沢田正,富沢圭吾
    • Organizer
      LIFE2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] 動的力学刺激環境によるiPS細胞の増殖,分化,組織構築制御と再生医療支援技術開発の可能性2019

    • Author(s)
      小沢田 正
    • Organizer
      ベンチャー創設支援フォーラム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] A bioreactor system for the cardiac differentiation of human iPS cells.2019

    • Author(s)
      S Yoshino, T Suenaga, Z Feng, T Kosawada, D Sato, T Nakamura, M Umezu
    • Organizer
      The 8th Meeting of the International Federation for Artificial Organs
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Investigation on the cardiomyocyte subtypes derived from human iPS cells on ventricular ECM hydrogels2019

    • Author(s)
      F Hamada, K Fujita, Z Feng, T Kosawada, D Sato, T Nakamura, Y Shiraishi, M Umezu.
    • Organizer
      The 8th Meeting of the International Federation for Artificial Organs
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Remarks] Kosawada "Biomechanics" Lab. Website

    • URL

      http://kosawada-lab.yz.yamagata-u.ac.jp/

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report 2019 Annual Research Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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