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Construction and functional expression of 3-dimensional vascularized liver tissue models by innovations in materials, processes, and devices

Research Project

Project/Area Number 18K18969
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 27:Chemical engineering and related fields
Research InstitutionChiba University

Principal Investigator

Yamada Masumi  千葉大学, 大学院工学研究院, 准教授 (30546784)

Project Period (FY) 2018-06-29 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords生体組織工学 / 肝細胞 / マイクロ流体デバイス / バイオマテリアル / 生物化学工学 / ハイドロゲル / 共培養 / 細胞培養 / 光架橋 / 水性2相系 / 生体材料 / 生物・生体工学 / プロセス工学
Outline of Final Research Achievements

Hepatocytes play vital roles in our body, including drug metabolism, blood purification, and production of serum proteins, and hence, hepatocytes are important in drug discovery research. However, when hepatocytes are isolated from the liver and cultured in vitro, their functions are rapidly degraded. In this study, we attempted to create a three-dimensional tissue models with vascular networks in order to optimize the function of hepatocytes in in vitro culture. To achieve this purpose, we developed novel materials such as porous hydrogels that can be applicable to perfusion culture, techniques to control the flow of medium and oxygen supply, and microfluidic devices that control the cell environment, and developed several key technologies that will potentially revolutionize liver tissue engineering.

Academic Significance and Societal Importance of the Research Achievements

本研究では,細胞を生きたまま導入できる多孔性のハイドロゲル材料を作製するための新規手法を開発したほか,コラーゲンなどのタンパク質成分からなる細胞培養用基材に対して微細加工を施すことによって,導入する肝細胞の機能や生存率を向上できることを明らかにした。また,酸素や栄養分の供給を向上するための潅流培養プロセス,またそれを実現するためのマイクロ流体デバイスの開発を行った。これらの結果を通して,生体において肝細胞を取り囲む環境を,生体外において再現するための技術を駆使することの重要性を示すことができた。本研究において得られた結果は,特に肝細胞をベースとする創薬研究に適用可能であると考えられる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (23 results)

All 2021 2020 2019 2018 Other

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (17 results) (of which Int'l Joint Research: 7 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] Flow-through Cell Culture System Using Microcavities Embedded in Spongelike PDMS Matrix2020

    • Author(s)
      Mai Takagi, Masumi Yamada, and Minoru Seki
    • Journal Title

      Proceedings of the 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences

      Volume: - Pages: 849-850

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] One-step Formation of Microporous Hydrogel Sponges Encapsulating Living Cells by Utilizing Bicontinuous Dispersion of Aqueous Polymer Solutions2019

    • Author(s)
      Aruto Hori, Yuki Watabe, Masumi Yamada, Yuya Yajima, Rie Utoh, and Minoru Seki
    • Journal Title

      ACS Applied Bio Materials

      Volume: 2 Issue: 5 Pages: 2237-2245

    • DOI

      10.1021/acsabm.9b00194

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fabrication of Continuous Micropores in Cell-encapsulating Hydrogels Using Densely-packed Microengineered Fibers2019

    • Author(s)
      Yoshimasa Minoda, Aruto Hori, Rie Utoh, Masumi Yamada, and Minoru Seki
    • Journal Title

      Proceedings of the 23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2019)

      Volume: - Pages: 326-327

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Formation of Pressurizable Hydrogel-based Vascular Tissue Models by Selective Gelation in Composite PDMS Channels2019

    • Author(s)
      Mayu Fukushi, Keita Kinoshita, Masumi Yamada, Yuya Yajima, Rie Utoh, and Minoru Seki
    • Journal Title

      RSC Advances

      Volume: 9 Issue: 16 Pages: 9136-9144

    • DOI

      10.1039/c9ra00257j

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fabrication of Microchannel Network‐Embedding Hydrogel Sponges for 3D Perfusion Culture of Mammalian Cells2018

    • Author(s)
      Aruto Hori, Yuki Watabe, Yuya Yajima, Rie Utoh, Masumi Yamada, and Minoru Seki
    • Journal Title

      Proc. MicroTAS 2018

      Volume: - Pages: 1428-1430

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 断片化コラーゲンマイクロファイバーの高効率調製とシート状組織形成への応用2021

    • Author(s)
      山中啓吾,鵜頭理恵,山田 真澄,関 実
    • Organizer
      化学工学会第86年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ポーラスマイクロウェル統合型流路を用いる肝細胞の3次元かん流培養系2021

    • Author(s)
      高木真惟,山田真澄,鵜頭理恵,関 実
    • Organizer
      2020年度シンポジウム:細胞アッセイ技術の現状と将来
    • Related Report
      2020 Annual Research Report
  • [Presentation] フロースルー多孔性チャンバーを利用したスフェロイドの灌流培養技術2020

    • Author(s)
      高木真惟,山田真澄,鵜頭理恵,関 実
    • Organizer
      化学とマイクロ・ナノシステム学会第42回研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] マイクロ流体デバイスを用いた細胞分離・培養・操作システムの開発2020

    • Author(s)
      山田真澄
    • Organizer
      化学とマイクロ・ナノシステム学会第42回研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 流路統合型多孔性マイクロウェルを利用した動物細胞の三次元的培養技術2020

    • Author(s)
      高木真惟,山田真澄,関 実
    • Organizer
      化学工学会第51回秋季大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Flow-through Cell Culture System Using Microcavities Embedded in Spongelike PDMS Matrix2020

    • Author(s)
      Mai Takagi, Masumi Yamada, and Minoru Seki
    • Organizer
      The 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2020)
    • Related Report
      2020 Annual Research Report
  • [Presentation] 光架橋性ゼラチンを用いた多孔性ハイドロゲルの微細加工と細胞培養2020

    • Author(s)
      蓑田義将,堀 有音,鵜頭理恵,山田真澄,関 実
    • Organizer
      化学工学会第85年会
    • Related Report
      2019 Research-status Report
  • [Presentation] ハイドロゲルスポンジを利用する肝細胞の3次元かん流培養系2020

    • Author(s)
      堀 有音,鵜頭理恵,山田真澄,関 実
    • Organizer
      2019年度シンポジウム:細胞アッセイ技術の現状と将来
    • Related Report
      2019 Research-status Report
  • [Presentation] Fabrication of Continuous Micropores in Cell-encapsulating Hydrogels Using Densely-packed Microengineered Fibers2019

    • Author(s)
      Yoshimasa Minoda, Aruto Hori, Rie Utoh, Masumi Yamada, and Minoru Seki
    • Organizer
      The 23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2019)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Preparation of Microporous Hydrogel Sponges for 3D Perfusion Culture of Mammalian Cells2019

    • Author(s)
      Aruto Hori, Masumi Yamada, Rie Utoh, and Minoru Seki
    • Organizer
      The 18th Asian Pacific Confederation of Chemical Engineering Congress (APCChE 2019)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 犠牲ファイバーを利用した細胞内包多孔性ハイドロゲルの作製と細胞機能評価2019

    • Author(s)
      蓑田義将,堀 有音,鵜頭理恵,山田真澄,関 実
    • Organizer
      第71回日本生物工学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 薬剤アッセイを目指したバイオマテリアルの精密加工と肝細胞培養2019

    • Author(s)
      山田真澄
    • Organizer
      日本分析化学会第68年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Preparation of Cell-encapsulating Hydrogel Sponges Using Bicontinuous Dispersion of Aqueous Polymer Solutions2018

    • Author(s)
      Aruto Hori, Yuki Watabe, Yuya Yajima, Rie Utoh, Masumi Yamada, and Minoru Seki
    • Organizer
      1st G'L'owing Polymer Symposium in KANTO (GPS-K 2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Preparation of Microvasculature-embedding Porous Hydrogels for 3D Cell Culture2018

    • Author(s)
      Aruto Hori, Yuki Watabe, Yuya Yajima, Rie Utoh, Masumi Yamada, and Minoru Seki
    • Organizer
      29th 2018 International Symposium on Micro-NanoMechatronics and Human Science (MHS 2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Facile Preparation of Cell-Embedding Hydrogel Sponges for 3D cell culture2018

    • Author(s)
      Aruto Hori, Masumi Yamada, Yuki Watabe, Yuya Yajima, Rie Utoh, and Minoru Seki
    • Organizer
      24th Symposium of Young Asian Biological Engineer’s Community (YABEC 2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Fabrication of Microchannel Network‐Embedding Hydrogel Sponges for 3D Perfusion Culture of Mammalian Cells2018

    • Author(s)
      Aruto Hori, Yuki Watabe, Yuya Yajima, Rie Utoh, Masumi Yamada, and Minoru Seki
    • Organizer
      The 22nd International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 共連続水性2相系を利用する多孔性ハイドロゲルの作製と3次元細胞培養2018

    • Author(s)
      堀 有音,渡部有紀,矢嶋祐也,鵜頭理恵,山田真澄,関 実
    • Organizer
      化学工学会室蘭大会 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Remarks] バイオプロセス化学研究室HP

    • URL

      http://chem.tf.chiba-u.jp/gacb01/

    • Related Report
      2020 Annual Research Report 2019 Research-status Report 2018 Research-status Report

URL: 

Published: 2018-07-25   Modified: 2022-12-28  

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