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Precise reconstruction of complex biological tissue by flexible processing of "porous" matrix

Research Project

Project/Area Number 20H02529
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 27040:Biofunction and bioprocess engineering-related
Research InstitutionChiba University

Principal Investigator

SEKI Minoru  千葉大学, 大学院工学研究院, 教授 (80206622)

Co-Investigator(Kenkyū-buntansha) 山田 真澄  千葉大学, 大学院工学研究院, 准教授 (30546784)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2022: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Keywords生体組織工学 / マイクロ流体デバイス / 微細加工 / コラーゲン / 肝細胞 / ハイドロゲル / バイオマテリアル / 細胞培養 / 幹細胞
Outline of Research at the Start

創薬や再生医療への応用のため,生体外で様々な3次元細胞培養系が提案されてきたが,生体組織と同等レベルの機能を発現しうる技術は開発途上にある。本研究では,「内部の管腔サイズや形状を自由に制御でき」,「細胞の機能発現を制御できる細胞外マトリックス成分によって構成され」,「内外に異なる細胞を均一導入できる」,多孔性ハイドロゲル材料を作製する革新的プロセスを確立する。得られた材料に幹細胞を導入し,効率的な分化誘導場としての応用を行う。また,肝臓等の階層的生体組織を精密に再構成し,最終的には,iPS細胞の分化誘導から薬剤アッセイまでをワンステップで実現できる多臓器連環型の薬剤評価システムの開発を目指す。

Outline of Final Research Achievements

In this study, we developed new processes to fabricate porous hydrogel materials that "can freely control the size and shape of the inner pores," "are composed of extracellular matrix (ECM) components that control cell survival, differentiation, and functions," and "can uniformly introduce multiple cell types into and out of the matrix". Using the obtained materials, we cultured hepatocytes, vascular cells, nerve cells, mesenchymal stem cells, etc., under dynamic environmental control by perfusion culture, and evaluated the effects on the function, proliferation, survival, and differentiation of these cells.

Academic Significance and Societal Importance of the Research Achievements

近年,細胞培養工学技術の発展にともない,各種幹細胞を始めとした種々のヒト細胞を容易に入手可能な状況となった。しかしながら,生体外において,生体と同等の細胞機能を発現させる技術は未だ発展の途上にある。本研究では,マトリックスの密度・組成を自在に変化でき,さらに内部の細胞に対して効率的な培養液を供給可能な多孔性のバイオマテリアルを形成し応用することで,薬剤の評価や生化学研究,再生医療に資する技術開発を行うこととした。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (42 results)

All 2023 2022 2021 2020 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 2 results) Presentation (31 results) (of which Int'l Joint Research: 9 results) Remarks (1 results)

  • [Journal Article] A Multiscale, Vertical-flow Perfusion System with Integrated Porous Microchambers for Upgrading Multicellular Spheroid Culture2023

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

      Lab on a Chip

      Volume: 23 Issue: 9 Pages: 2257-2267

    • DOI

      10.1039/d3lc00168g

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expansion of Chinese Hamster Ovary Cells via a Loose Cluster-assisted Suspension Culture Using Cell-sized Gelatin Microcarriers2023

    • Author(s)
      Yuken Hasebe, Masumi Yamada*, Rie Utoh, and Minoru Seki
    • Journal Title

      Journal of Bioscience and Bioengineering,

      Volume: 135 (5) Issue: 5 Pages: 417-422

    • DOI

      10.1016/j.jbiosc.2023.02.008

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fragmented Collagen Microfiber-assisted Formation of Skin Tissue Models with Tunable Cell/Matrix Densities2022

    • Author(s)
      Yuri Shimoda, Keigo Yamanaka, Masumi Yamada, Rie Utoh, and Minoru Seki
    • Journal Title

      Proceedings of the 26th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2022)

      Volume: 1 Pages: 324-325

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Formation of 3D Tissues of Primary Hepatocytes Using Fibrillized Collagen Microparticles as Intercellular Binders2022

    • Author(s)
      Akihiro Morita, Masumi Yamada, Rie Utoh, Kanta Momiyama, Hideki Iwadate, and Minoru Seki
    • Journal Title

      Journal of Bioscience and Bioengineering

      Volume: 133 Issue: 3 Pages: 265-272

    • DOI

      10.1016/j.jbiosc.2021.11.009

    • NAID

      210000159518

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Polyanion-induced, microfluidic engineering of fragmented collagen microfibers for reconstituting extracellular environments of 3D hepatocyte culture2021

    • Author(s)
      Utoh Rie、Enomoto Sakiko、Yamada Masumi、Yamanaka Keigo、Yajima Yuya、Furusawa Kazuya、Seki Minoru
    • Journal Title

      Materials Science and Engineering: C

      Volume: 129 Pages: 112417-112417

    • DOI

      10.1016/j.msec.2021.112417

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dually Connected Double-Capillary Device for Fabricating Vasculature-Mimetic Microtubes2021

    • Author(s)
      Kanta Momiyama, Mai Takagi, Taiga Mitsuda, Masumi Yamada, Rie Utoh, and Minoru Seki
    • Journal Title

      Proceedings of the 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2021)

      Volume: 1 Pages: 907-908

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Microfluidic Production of Collagen Sheet-based Cell Envelope for Floating Sandwich Culture of Hepatocytes2021

    • Author(s)
      Mai Takagi, Kanta Momiyama, Masumi Yamada, Rie Utoh, and Minoru Seki
    • Journal Title

      Proceedings of the 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2021)

      Volume: 1 Pages: 273-274

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Accelerated Formation of Capillary Bed Structures Using Fragmented Sacrificial Microfibers2021

    • Author(s)
      Mizuki Hirata, Masumi Yamada, Rie Utoh, and Minoru Seki
    • Journal Title

      Proceedings of the 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2021)

      Volume: 1 Pages: 111-112

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sacrificial Alginate-assisted Microfluidic Engineering of Cell-supportive Protein Microfibers for Hydrogel-based Cell Encapsulation2020

    • Author(s)
      Kotone Saeki, Hisataka Hiramatsu, Ayaka Hori, Yu Hirai, Masumi Yamada*, Rie Utoh, and Minoru Seki
    • Journal Title

      ACS Omega

      Volume: 5 Issue: 34 Pages: 21641-21650

    • DOI

      10.1021/acsomega.0c02385

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 (MicroTAS 2020)

      Volume: 1 Pages: 849-850

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] 配向性コラーゲンファイバー束を用いた神経細胞の伸展制御2023

    • Author(s)
      長谷部友権,山田真澄,鵜頭理恵,関 実
    • Organizer
      化学工学会第88年会,東京農工大学 小金井キャンパスおよびオンライン
    • Related Report
      2022 Annual Research Report
  • [Presentation] 断片化マイクロファイバーを用いるマイクロ流路内毛細血管網の迅速形成2022

    • Author(s)
      平田瑞季,山田真澄,鵜頭理恵,関 実
    • Organizer
      化学工学会新潟大会2022, 朱鷺メッセ 新潟コンベンションセンター
    • Related Report
      2022 Annual Research Report
  • [Presentation] 連結二重管デバイスを用いたコラーゲンハイドロゲルチューブの作製とその応用2022

    • Author(s)
      籾山貫太,高木真惟,蜜田大雅,山田真澄,鵜頭理恵,関 実
    • Organizer
      化学工学会新潟大会2022, 朱鷺メッセ 新潟コンベンションセンター
    • Related Report
      2022 Annual Research Report
  • [Presentation] 逆コロイド結晶を統合した液滴形成デバイスを用いる微粒子の調製2022

    • Author(s)
      増山将太,逸見るな,佐藤丈流,山田真澄,関 実
    • Organizer
      化学工学会新潟大会2022, 朱鷺メッセ 新潟コンベンションセンター
    • Related Report
      2022 Annual Research Report
  • [Presentation] コラーゲンファイバーを用いる流体デバイス統合型多層皮膚モデルの作製2022

    • Author(s)
      霜田有里,山中啓吾,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46回研究会,アスティとくしま
    • Related Report
      2022 Annual Research Report
  • [Presentation] 断片化コラーゲンマイクロファイバーを用いる多層ヒト皮膚モデルの形成2022

    • Author(s)
      霜田有里,山中啓吾,山田真澄,鵜頭理恵,関 実
    • Organizer
      化学工学会第53回秋季大会,信州大学 長野(工学)キャンパスおよびオンライン
    • Related Report
      2022 Annual Research Report
  • [Presentation] 流路統合型スピナレットを用いる細胞導入コラーゲンチューブの作製2022

    • Author(s)
      高木真惟,籾山貫太,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45回研究会,中央大学 後楽園キャンパスおよびオンライン
    • Related Report
      2022 Annual Research Report
  • [Presentation] スフェロイドへの培地供給を効率化するフロースルー多孔性チャンバーの開発2022

    • Author(s)
      高木真惟,山田真澄,鵜頭理恵,関 実
    • Organizer
      第29回HAB研究機構学術年会,昭和大学 上條記念館およびオンライン
    • Related Report
      2022 Annual Research Report
  • [Presentation] 犠牲マイクロファイバーを用いる毛細血管モデルの迅速形成2022

    • Author(s)
      平田瑞季,山田真澄,鵜頭理恵,関 実
    • Organizer
      第29回HAB研究機構学術年会,昭和大学 上條記念館およびオンライン
    • Related Report
      2022 Annual Research Report
  • [Presentation] Rapid preparation of blood capillary networks using fragmented cell-encapsulating hydrogel microfibers as sacrificial material2022

    • Author(s)
      Mizuki Hirata, Masumi Yamada, Rie Utoh, and Minoru Seki
    • Organizer
      The 27th Symposium of Young Asian Biological Engineers’ Community (YABEC 2022), Online
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fragmented Collagen Microfiber-assisted Formation of Skin Tissue Models with Tunable Cell/Matrix Densities2022

    • Author(s)
      Yuri Shimoda, Keigo Yamanaka, Masumi Yamada, Rie Utoh, and Minoru Seki
    • Organizer
      The 26th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2022), Online, and Hangzhou International Expo Center, Hangzhou, China
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Chondrogenic Differentiation of MSCs Using Fibrillized Collagen Microparticles as an Intercellular Binder2022

    • Author(s)
      Fumika Sano, Masumi Yamada, Rie Utoh, and Minoru Seki
    • Organizer
      Symposium on Biomeducal Engineering (ACB-ISBE 2022), Merusaka Hotel Bali, Indonesia, and Online
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fabrication and Morphology Control of Collagen Tubes as Scaffolds for Cell Culture Using Multilayer Microfluidic Devices2022

    • Author(s)
      Mai Takagi, Kanta Momiyama, Masumi Yamada, Rie Utoh, and Minoru Seki
    • Organizer
      15th Asian Congress on Biotechnology in conjunction with 7th International Symposium on Biomeducal Engineering (ACB-ISBE 2022), Merusaka Hotel Bali, Indonesia, and Online
    • Related Report
      2022 Annual Research Report
  • [Presentation] 二重管連結デバイスを用いた血管模倣コラーゲンマイクロチューブの作製2022

    • Author(s)
      籾山貫太,高木真惟,蜜田大雅,山田真澄,鵜頭理恵,関 実
    • Organizer
      化学工学会第87年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 細胞サイズゼラチン微粒子をキャリアとするCHO細胞の振とう培養系2022

    • Author(s)
      長谷部友権,山田真澄,鵜頭理恵,関 実
    • Organizer
      化学工学会第87年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 断片化マイクロファイバーを利用した毛細血管導入ハイドロゲルの微細加工2021

    • Author(s)
      平田瑞季,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44回研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] セルサイズゼラチン微粒子をキャリアとするCHO細胞の振とう培養系2021

    • Author(s)
      長谷部友権,山田真澄,鵜頭理恵,関 実
    • Organizer
      第73回日本生物工学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 断片化犠牲マイクロファイバー導入による毛細血管網のマイクロ流路内形成2021

    • Author(s)
      平田瑞季,山田真澄,鵜頭理恵,関 実
    • Organizer
      化学工学会第52回秋季大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 浮遊型サンドイッチ培養のためのコラーゲンベース細胞包埋シートの作製2021

    • Author(s)
      高木真惟,籾山貫太,山田真澄,鵜頭理恵,関 実
    • Organizer
      化学工学会第52回秋季大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 多孔性基材を組み込んだ微小流路を用いる肝細胞のかん流培養系2021

    • Author(s)
      高木真惟,山田真澄,鵜頭理恵,関 実
    • Organizer
      生物工学若手研究者の集い 夏のセミナー2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] フロースルー多孔性チャンバーを用いる動物細胞の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
      化学工学会秋田大会2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] Microengineered Porous Culture Chambers for Direct Medium Supply to Multicellular Spheroids of Hepatocytes2021

    • Author(s)
      Mai Takagi, Masumi Yamada, Rie Utoh, and Minoru Seki
    • Organizer
      The 26th Symposium of Young Asian Biological Engineers’ Community (YABEC 2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Microfluidic Production of Collagen Sheet-based Cell Envelope for Floating Sandwich Culture of Hepatocytes2021

    • Author(s)
      Mai Takagi, Kanta Momiyama, Masumi Yamada, Rie Utoh, and Minoru Seki
    • Organizer
      The 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Dually Connected Double-Capillary Device for Fabricating Vasculature-Mimetic Microtubes2021

    • Author(s)
      Kanta Momiyama, Mai Takagi, Taiga Mitsuda, Masumi Yamada, Rie Utoh, and Minoru Seki
    • Organizer
      The 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Accelerated Formation of Capillary Bed Structures Using Fragmented Sacrificial Microfibers2021

    • Author(s)
      Mizuki Hirata, Masumi Yamada, Rie Utoh, and Minoru Seki
    • Organizer
      The 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Gelatin Microparticles Prepared by Solvent Extraction Process for Suspension Culture of Mammalian Cells2021

    • Author(s)
      Yuken Hasebe, Masumi Yamada, Rie Utoh, and Minoru Seki
    • Organizer
      The 8th Asian Particle Technology Symposium (APT2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [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] 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] 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] 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] 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
    • Int'l Joint Research
  • [Remarks] 千葉大学 工学部共生応用化学コース バイオプロセス化学研究室

    • URL

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

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

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