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Construction of a multi-organ interaction model via the controlled vascularisation of modular organoids

Research Project

Project/Area Number 21K18048
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 90110:Biomedical engineering-related
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

KOH Isabel Siew Yin  国立研究開発法人理化学研究所, 開拓研究本部, 特別研究員 (90868415)

Project Period (FY) 2021-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsOrgan-on-a-Chip / Organoid / 3D culture / Organ-organ interaction / Organ-on-a-chip / Tissue interaction / Blood-brain barrier / Cube device / Multi-directional / Vascularisation / オルガノイド血管形成
Outline of Research at the Start

In vitroモデルにおいて臓器間相互作用の重要性がますます認識されており、OOCに複数のオルガノイドを統合することに関心が高まっている。そこで本研究では、複数のモジュール化されたオルガノイドの任意位置に血管新生を形成し、チップ内で各モジュールを組み合わせることによりオルガノイド間のグローバルな多臓器連関システムを構築することを目標とする。モジュール内任意位置にオルガノイド内部へと貫通する血管チャネルを導入し、人工的に設計された流体チップの流路に接合することで、複数のオルガノイドをつなげた臓器連関システムを目指す。

Outline of Final Research Achievements

Organoid and Organ-on-a-Chip (OoC) technologies are currently being advanced to replicate the human body in the laboratory, but it is still difficult to combine both technologies together. In this research, two methods to control the seeding position and pattern of cells in a CUBE culture device were developed: (1) 3D bioprinting of dissolvable carbohydrate glass mould to create complex patterns in hydrogel, and (2) 3D printed resin-based mould to create simple seeding pocket in hydrogel. Due to the modularity of the CUBE device, the cells can then easily be integrated with OoC devices to simulate culture conditions similar to that in the human body. This was demonstrated by culturing cells with a gradient of growth factors from opposing directions, similar to the signalling gradients in vivo that guide cell differentiation into different tissues or organs in the body.

Academic Significance and Societal Importance of the Research Achievements

The methods developed in this research can help bridge the gap between organoid and OoC researchers, leading to the generation of more sophisticated organoids that can mimic human organs, which would be useful in studying human disease mechanisms and drug treatment.

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (13 results)

All 2023 2022 2021 Other

All Int'l Joint Research (1 results) Journal Article (3 results) (of which Open Access: 3 results,  Peer Reviewed: 2 results) Presentation (7 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] University of Cambridge/MRC Laboratory of Molecular Biology(英国)

    • Related Report
      2022 Annual Research Report
  • [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] 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] 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 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Gradient Culture Platform to Generate Asymmetric Organoids with Two Locally Differentiated Regions2023

    • Author(s)
      Isabel Koh, Masaya Hagiwara
    • Organizer
      RIKEN BDR-CuSTOM Joint Organoid Symposium
    • Related Report
      2022 Annual Research Report
  • [Presentation] 成長因子勾配によるオルガノイドの分化を制御するCube-in-Chipプラットフォーム2023

    • Author(s)
      Isabel Koh, Masaya Hagiwara
    • Organizer
      Japanese Society for Regenerative Medicine
    • Related Report
      2022 Annual Research Report
  • [Presentation] Development of an in vitro Platform to Control iPSC Differentiation by Morphogen Gradient2022

    • Author(s)
      Isabel Koh, Masaya Hagiwara
    • Organizer
      Japan Neuroscience Society Annual Meeting
    • Related Report
      2022 Annual Research Report
  • [Presentation] Cube-in-Chip: An in vitro Platform to Control Organoid Differentiation by Morphogen Gradient2022

    • Author(s)
      Isabel Koh, Masaya Hagiwara
    • Organizer
      Development Journal Meeting 2022 - From Stem Cells to Human Development
    • Related Report
      2022 Annual Research Report
  • [Presentation] Designing Organoid Architecture: Introducing an Integrative Platform to Control Cellular Distribution, ECM Environment, and Morphogen Gradient in Organoid Culture2021

    • Author(s)
      Isabel Koh, Kasinan Suthiwanich, Atsushi Takano, Masaya Hagiwara
    • Organizer
      The Molecular Biology Society of Japan
    • Related Report
      2021 Research-status Report
  • [Presentation] BBB-on-a-Chip Model by Integration of Tissue-in-a-Cube with Fluidic Device2021

    • Author(s)
      Isabel Koh, Waki Sekine, Masaya Hagiwara
    • Organizer
      CHEMINAS
    • Related Report
      2021 Research-status Report
  • [Presentation] Next generation organ-on-a-chip platform: Merging modular 3D tissue-in-a-cube with microfluidics for a blood-brain barrier (BBB) model2021

    • Author(s)
      Isabel Koh, Masaya Hagiwara
    • Organizer
      The Japanese Society for the Study of Xenobiotics
    • Related Report
      2021 Research-status Report
  • [Remarks] Human Biomimetic System RIKEN Hakubi Research Team

    • URL

      https://hbms.riken.jp/

    • Related Report
      2022 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

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Published: 2021-04-28   Modified: 2024-01-30  

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