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Dynamic analysis of tissue development by 3D culture platform

Research Project

Project/Area Number 21H01299
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 20020:Robotics and intelligent system-related
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Hagiwara Masaya  国立研究開発法人理化学研究所, 開拓研究本部, 理研白眉研究チームリーダー (00705056)

Co-Investigator(Kenkyū-buntansha) 稲木 美紀子  大阪大学, 大学院理学研究科, 講師 (10747679)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2023: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2022: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Keywordsオルガノイド / 培養環境制御 / 三次元培養 / 組織間相互作用 / 流体チップ / 培養制御 / 4Dイメージング / 体軸形成 / Gradient / 空間局在制御 / 三次元イメージング / 組織形成 / 三次元制御 / 細胞行動 / 細胞ーECM相互作用 / 細胞パターニング / ダイナミクス計測 / 4Dイメージング
Outline of Research at the Start

生物の組織形成は非常に多くの細胞が絡みあった一つのシステムであり,場に働くダイナミクスを計測することは組織形成システムを理解する上で必要不可欠である.そこで本研究では,従来直接計測が困難であった組織形成時に場に働くダイナミクスを,3次元培養実験系における制御・計測・情報技術を高度に融合することにより解析することを目的とする.当該研究者が開発した培養Cubeを基軸に,集団と細胞のマルチスケールな挙動をイメージング可能な新たな計測系を構築し,さらに三次元細胞環境を制御可能な手法を確立し,生体組織形成において細胞が従っている根底のルールを解明することを目指す.

Outline of Final Research Achievements

In the formation of mini-organs (organoids) from stem cells, it is common to culture a collection of individually dissociated cells that have lost their positional information under a single condition, relying on the autonomous formation of cells. As a result, the morphology often deviates significantly from that of the original organ. In this research project, we have established a method to control the positional information of cells, the spatial information of the extracellular matrix, and the concentration gradients of humoral factors by incorporating multiple engineering technologies into the CUBE-type culture device we developed. This allows us to provide an asymmetric environment in the culture, thereby enabling the intentional induction of autonomous formation from cells to tissues.

Academic Significance and Societal Importance of the Research Achievements

本研究課題において開発した手法は、オルガノイドに体軸方向を付与し、より高次な臓器へ成長させるための基盤技術になることが期待できる。実験自体はシンプルなCUBE型培養器に落とし込んでおり、ポンプなどのような外部装置を一切排除して培養できるように落とし込んだため、高い汎用性が期待できる。本技術によりオルガノイドの高次形態を達成することにより、より高精度な創薬モデルとして活用することが期待でき、またデザインされた臓器連関への道筋も見えてくる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (36 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (6 results) Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 6 results) Presentation (18 results) (of which Int'l Joint Research: 5 results,  Invited: 9 results) Remarks (2 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 2 results)

  • [Int'l Joint Research] Cambridge University/King's College London(英国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Max Planck Institute, CBG(ドイツ)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] EPFL(スイス)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] Cambridge University(英国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Yale University(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Cincinnati Children's hospital(米国)

    • Related Report
      2022 Annual Research Report
  • [Journal Article] Modular tissue-in-a-CUBE platform to model blood-brain barrier (BBB) and brain interaction2024

    • Author(s)
      Koh Isabel、Hagiwara Masaya
    • Journal Title

      Communications Biology

      Volume: 7 Issue: 1 Pages: 177-177

    • DOI

      10.1038/s42003-024-05857-8

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Localization of Multiple Hydrogels with MultiCUBE Platform Spatially Guides 3D Tissue Morphogenesis In Vitro2023

    • Author(s)
      Suthiwanich Kasinan、Hagiwara Masaya
    • Journal Title

      Advanced Materials Technologies

      Volume: 8 Issue: 4 Pages: 2201660-2201660

    • DOI

      10.1002/admt.202201660

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gradient to sectioning CUBE workflow for the generation and imaging of organoids with localized differentiation2023

    • Author(s)
      Koh Isabel、Hagiwara Masaya
    • Journal Title

      Communications Biology

      Volume: 6 Issue: 1

    • DOI

      10.1038/s42003-023-04694-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modular Tissue-in-a-CUBE Platform to Model Blood-brain-Barrier (BBB) and Brain Interaction2023

    • Author(s)
      Koh Isabel、Hagiwara Masaya
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/2023.02.25.529996

    • Related Report
      2022 Annual Research Report
    • Open Access
  • [Journal Article] 3D Culture Platform for Enabling Large-Scale Imaging and Control of Cell Distribution into Complex Shapes by Combining 3D Printing with a Cube Device2022

    • Author(s)
      Atsushi Takano, Isabel Koh, Masaya Hagiwara
    • Journal Title

      Micromachines

      Volume: 13 Issue: 2 Pages: 156-156

    • DOI

      10.3390/mi13020156

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Weakening of resistance force by cell-ECM interactions regulate cell migration directionality and pattern formation2021

    • Author(s)
      Masaya Hagiwara, Hisataka Maruyama, Masakazu Akiyama, Isabel Koh, Fumihito Arai
    • Journal Title

      Communications Biology

      Volume: 4 Issue: 1 Pages: 808-808

    • DOI

      10.1038/s42003-021-02350-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Integration platform for organoids and organ-on-a-Chip by modularized technologies to control and sensing microenvironments with CUBE2023

    • Author(s)
      Isabel Koh, Kasinan Suthiwanich, Masaya Hagiwara
    • Organizer
      MPS World Summit 2024
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Replicating Organ-Organ (BBB-Brain) Interaction with Modular Tissue-in-a-CUBE Chip2023

    • Author(s)
      Isabel Koh, Masaya Hagiwara
    • Organizer
      MPS World Summit 2024
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Design and control of in vitro microenvironments with simple CUBE device to achieve organoid architecture2023

    • Author(s)
      Masaya Hagiwara
    • Organizer
      EMBO | EMBL Symposium: Organoids: modelling organ development and disease in 3D culture
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Control of collective cell migration by cell-ECM interactions2023

    • Author(s)
      Masaya Hagiwara
    • Organizer
      生物物理学会年会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Organoid platform: Design and control of microenvironments to achieve organ architecture2023

    • Author(s)
      Masaya Hagiwara
    • Organizer
      2023 RIKEN BDR - CuSTOM Joint Organoid Symposium
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 細胞周り微小環境制御によるオルガノイド形態制御2022

    • Author(s)
      萩原将也
    • Organizer
      R031ハイブリッド量子ナノ技術委員会 第8回研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] MPSとオルガノイドを繋ぐ生体模倣システムの構築2022

    • Author(s)
      萩原将也
    • Organizer
      情報計算科学生物学会(CBI学会)2022年大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] オルガノイド培養プラットフォーム:微小環境制御によるオルガノイド形態制御2022

    • Author(s)
      萩原将也
    • Organizer
      細胞を創る研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] MPSとオルガノイドを繋ぐ次世代in vitroモデルの構築2022

    • Author(s)
      萩原将也
    • Organizer
      日本薬剤学会第37回年会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Guiding anisotropic morphogenesis in vitro through hydrogel localization with MultiCUBE2022

    • Author(s)
      Kasinan Suthiwanich, Masaya Hagiwara
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Gradient-in-CUBE to Control Organoid Differentiation and Sample Orientation during Analysis2022

    • Author(s)
      Isabel Koh, Masaya Hagiwara
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 培養制御プラットフォームによるオルガノイド形態制御2022

    • Author(s)
      萩原将也、Isabel Koh, Kasinan Suthiwanich
    • Organizer
      第22回日本再生医療学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] オルガノイド培養プラットフォーム:体軸形成から切片イメージまでシームレスなワークフロー2022

    • Author(s)
      Isabel Koh, Masaya Hagiwara
    • Organizer
      第22回日本再生医療学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Design and control of microenvironments to achieve organoid architecture.2022

    • Author(s)
      Masaya Hagiwara, Isabel Koh, Kasinan Suthiwanich
    • Organizer
      From stem cells to human development
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cube-in-Chip: An in vitro Platform to Control Organoid Differentiation by Morphogen Gradient2022

    • Author(s)
      Isabel Koh, Masaya Hagiwara
    • Organizer
      From stem cells to human development
    • Related Report
      2022 Annual Research Report
  • [Presentation] Designing Organoid Architecture2021

    • Author(s)
      I. Koh, K. Suthiwanich, A. Takano, M. Hagiwara
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Design and control of cellular dynamics to reconstruct sophisticated 3D tissues2021

    • Author(s)
      M. Hagiwara, I. Koh, K. Suthiwanich, A. Tkano
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 次世代オルガノイド開発のための培養環境設計・制御手法の構築2021

    • Author(s)
      萩原将也
    • Organizer
      第39回日本ロボット学会学術講演会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Remarks] 研究室ウェブサイト

    • URL

      https://hbms.riken.jp/

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
  • [Remarks]

    • URL

      https://hbms.riken.jp/

    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 観察用切片作製用のブロック、及びその利用2023

    • Inventor(s)
      萩原将也、Isabel Koh
    • Industrial Property Rights Holder
      萩原将也、Isabel Koh
    • Industrial Property Rights Type
      特許
    • Filing Date
      2023
    • Related Report
      2023 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 観察用切片作製用のブロック、及びその利用2022

    • Inventor(s)
      萩原将也、コウイザベルシュイン
    • Industrial Property Rights Holder
      理化学研究所
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2022-140997
    • Filing Date
      2022
    • Related Report
      2022 Annual Research Report
  • [Patent(Industrial Property Rights)] 細胞培養容器、観察装置、顕微鏡、培養方法及び観察方法2021

    • Inventor(s)
      萩原将也
    • Industrial Property Rights Holder
      理化学研究所
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 細胞培養容器、固定具、観察装置、顕微鏡および観察方法2021

    • Inventor(s)
      萩原将也
    • Industrial Property Rights Holder
      理化学研究所
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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