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Co-culture model of intestinal epithelial cells and micro-biota on-a-chip

Research Project

Project/Area Number 18K19905
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 90:Biomedical engineering and related fields
Research InstitutionTokyo Institute of Technology

Principal Investigator

TAGAWA YOH-ICHI  東京工業大学, 生命理工学院, 准教授 (70262079)

Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords腸管 / 腸内細菌 / 共培養 / 代謝 / 毒性 / 腸管チップ / マイクロ流体デバイス / 腸管上皮細胞 / 腸管モデル / 腸管組織 / 大腸炎モデル / 腸管培養モデル / 嫌気培養 / 細菌叢
Outline of Final Research Achievements

A device, equipping two independent channels separated by a porous membrane where intestinal epithelial (C2BBe1) cells were cultured, and electrodes for measurement of TEER was invented in this study. After C2BBe1 cells formed tight junction in the whole area on the membrane E. coli was supplied from the upper channel. The tight junction of C2BBe1 cells could be maintained with E.Coli for 3 days by the adequate flow rate, however failed by the static condition. Furthermore, L. murinus was succeeded to be co-cultured in the above co-culture fluidic device. On the other hand, after macrophage cell line RAW264 cells were supplied from the lower channel of C2BBe1 cell-culture device, E.Coli was inoculated in the lower channel. The tight junction was disrupted by the E.Coli, but maintained without the E.Coli. By using this system, it is expected to establish not only co-culturing system of intestinal micro-biota and intestinal epithelial tissue on a chip but also enteritis culture model.

Academic Significance and Societal Importance of the Research Achievements

全身の疾患と腸内細菌叢の関連に関して詳細な研究は極めて難しく、腸内細菌と宿主の関係を調べるための培養系は確立されていない。腸内細菌を単純嫌気培養する手法は報告されているが、腸管組織がないので腸内細菌による代謝物質がどのように体内に取り込まれているのかまでは解析できなかった。しかし、本研究で開発した腸管組織チップでは、腸内細菌を一定数で24時間以上維持することが可能である。薬物や消化物質が腸内細菌により代謝された後、腸管組織を経由して体内に輸送されることを本腸管組織チップで解析することができることは、栄養学や毒性学において大いに役立つと思われる。

Report

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

    (39 results)

All 2020 2019 2018

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (33 results) (of which Int'l Joint Research: 14 results,  Invited: 5 results)

  • [Journal Article] Acetaminophen-induced hepatotoxicity of cultured hepatocytes depends on timing of isolation from light-cycle controlled mice.2020

    • Author(s)
      Koji Moriya, Miho Tamai, Takumi Koga, Toshiaki Tanaka and Yoh-ichi Tagawa.
    • Journal Title

      Genes to Cells

      Volume: 25 Issue: 4 Pages: 257-269

    • DOI

      10.1111/gtc.12755

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Study of time-dependent pharmacokinetics of mouse embryonic stem cell-derived cardiomyocytes for drug screening2020

    • Author(s)
      2.Zhen Qi, Misato Kamoshida, Miho Tamai, Masamichi Hirose, and Yoh-ichi Tagawa
    • Journal Title

      Translational and Regulatory Sciences

      Volume: 2 Issue: 1 Pages: 7-13

    • DOI

      10.33611/trs.2_7

    • NAID

      130007808420

    • ISSN
      2434-4974
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acorbine, a Corbicula japonica-derived tripeptide containing non-proteinogenic amino acids, suppresses ethanol-induced liver injury.2020

    • Author(s)
      Tamai M, Uchisawa H, Saito Y, Matsue H, Kawase M, Naraoka T, Tagawa Y
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 522(3) Issue: 3 Pages: 580-584

    • DOI

      10.1016/j.bbrc.2019.11.131

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Contribution of rat embryonic stem cells to xenogeneic chimeras in blastocyst or 8-cell embryo injection and aggregation.2019

    • Author(s)
      Okumura H, Nakanishi A, Toyama S, Yamanoue M, Yamada K, Ukai A, Hashita T, Iwao T, Miyamoto T, Tagawa YI, Hirabayashi M, Miyoshi I, Matsunaga T.
    • Journal Title

      Xenotransplantation

      Volume: 26(1) Issue: 1

    • DOI

      10.1111/xen.12468

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A highly bioactive Lys-deficient IFN leads to a site-specific di-PEGylated IFN with equivalent bioactivity to that of unmodified IFN-α2b2018

    • Author(s)
      T. Imada, K. Moriya, M. Uchiyama, M. Hitotsuyanagi, A. Masuda, S. Ayukawa, Y. Tagawa, N. Dohmae, M. Yamamura, D. Kiga
    • Journal Title

      ACS Synthetic Biology

      Volume: 7 Issue: 11 Pages: 2537-2546

    • DOI

      10.1021/acssynbio.8b00188

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of a nano-scale fine hole pattern on the differentiation of RAW264.7 cells into osteoclasts2018

    • Author(s)
      R. Takata, T. Akasaka, M. Tamai, Y. Yoshimura, T. Taira, H. Miyaji, Y. Tagawa, S. Yamagata, J. Iida, Y. Yoshida
    • Journal Title

      Digest Journal of Nanomaterials and Biostructures

      Volume: 13 Issue: 3 Pages: 451-458

    • DOI

      10.1016/j.jbiosc.2017.10.001

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Intestinal Epithelium and Bacteria on a Chip2020

    • Author(s)
      Yoh-ichi Tagawa
    • Organizer
      The 5th Annual Meeting of Living Systems Design Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Immune-cell response culture model derived from murine embryonic stem cells for drug induced liver injury2020

    • Author(s)
      Miho Tamai and Yoh-ichi Tagawa
    • Organizer
      The 5th Annual Meeting of Living Systems Design Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of a microfluidic device measuring drug absorption and permeability of intestinal epithelial cells2020

    • Author(s)
      Aika Okazaki, M. Nakazawa, Y. Fujiyama, Miho Tamai, and Yoh-ichi Tagawa
    • Organizer
      The 5th Annual Meeting of Living Systems Design Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Multidimensional co-culture of intestinal epithelial cell, macrophage and bacteria for IBD model on microfluidic device2020

    • Author(s)
      M. Tsuda, H, Shindo, M. Nakazawa, Y. Fujiyama, E. Ozeki, M. Tamai, and Y. Tagawa
    • Organizer
      The 5th Annual Meeting of Living Systems Design Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Formation of Turing patterns in a synthetic bacterial population under more natural environment2020

    • Author(s)
      Takato Saito, Moe Takahashi, Soh Tsuruta, Hajime Fujita, Akito Machida, Ryoto Matsuda, NG SIN YING, VOON YAN MING, Yusuke Kato, Yuumi Kitano, Ayano Tabira, Nobuhiro Hayashi, Masayuki Yamamura, and Yoh-ichi Tagawa
    • Organizer
      The 5th Annual Meeting of Living Systems Design Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] In vitro liver tissue model of human iPS cell-derived hepatocytes and HUVEC networks2020

    • Author(s)
      Hong JinHo, Miho Tamai, Taiki Satoh,and Yoh-ichi Tagawa
    • Organizer
      The 5th Annual Meeting of Living Systems Design Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cartilage tissue construction in microbial biopolymer polylactic acid P (DLA-co-3HA)2020

    • Author(s)
      M. Qiu, Y. Kawamura, A. Hiroe, S. Taguchi, Y. Tagawa
    • Organizer
      The 5th Annual Meeting of Living Systems Design Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Artificial control of circadian rhythm and production of clock fluorescent protein2020

    • Author(s)
      Li Jialong, Qi Zhen, Miki Imanishi, Yoh-ichi Tagawa
    • Organizer
      The 5th Annual Meeting of Living Systems Design Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel artificial transcription system-synchronized circadian rhythm in mouse ES cell-derived cardiomyocyte culture model2020

    • Author(s)
      Zhen Qi, Miho Tamai, Miki Imanishi, and Yoh-ichi Tagawa
    • Organizer
      The 5th Annual Meeting of Living Systems Design Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of central nervous system tissue chip derived from mouse ES cells2020

    • Author(s)
      Tomoya Abe, Kazumasa Takahashi, and Yoh-chi Tagawa
    • Organizer
      The 5th Annual Meeting of Living Systems Design Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 哺乳類の合成生物学のためのマイクロ流体デバイス技術2019

    • Author(s)
      Y. Tagawa
    • Organizer
      実験動物代替法学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 動物実験代替法のための培養モデルにおける必須要素‐組織チップによる哺乳類合成生物‐2019

    • Author(s)
      田川陽一
    • Organizer
      CBI学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ラウンドテーブルディスカッション2019

    • Author(s)
      田川陽一、平藤衛ら
    • Organizer
      第1回オープンフォーラムSingle Cell Analysis, いま・これから
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 動物実験代替法システムとしての組織チップの開発-生命とは何かを理解するための合成生物学-2019

    • Author(s)
      田川陽一
    • Organizer
      JMACバイオ計測技術コンソーシアム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Inflammatory liver disease culture model derived from murine ES cells in consideration of an immune-cell response2019

    • Author(s)
      Miho Tamai and Yoh-ichi Tagawa
    • Organizer
      Tissue Engineering and Regenerative Medicine International AP
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 臓器チップの最新動向と今後の展望‐動物実験代替法の実現を目指した人工生命体培養モデル‐2019

    • Author(s)
      田川陽一
    • Organizer
      新化学技術者協会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Circadian oscillators during heart tissue differentiation of mouse embryonic stem cells2019

    • Author(s)
      Zhen Qi, Misato Kamoshida, Miho Tamai, Yoh-ichi Tagawa
    • Organizer
      International Society for Stem Cell Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Human iPS Cell-derived Liver-on-a-Chip for Virus Infection2019

    • Author(s)
      Taiki Satoh, Miho Tamai, Yoichi Fujiyama, Yoh-ichi Tagawa
    • Organizer
      Organ-on-a-chip 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] B型肝炎ウイルスの感染・増殖評価系へ向けたヒトiPS細胞由来肝組織モデルの構築と流体デバイスの開発2019

    • Author(s)
      佐藤 敦紀、アン ソンホ、玉井 美保、藤山 陽一、中島 謙治、酒井 聡、鈴木 哲朗、田川 陽一
    • Organizer
      肝細胞研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] マウス肝臓プロテオミクスによる肝細胞分化機構の解明2019

    • Author(s)
      野村舞、田川陽一、青木秀年、林宣宏
    • Organizer
      肝細胞研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 哺乳類のデザイン生命工学2019

    • Author(s)
      田川陽一
    • Organizer
      第4回デザイン生命工学研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 腸管上皮細胞と大腸菌の共培養2019

    • Author(s)
      田川陽一、進藤寛将、中澤杜浩、小関英一、藤山陽一、三宅力、米田恭子
    • Organizer
      第13回長野ミーティング
    • Related Report
      2018 Research-status Report
  • [Presentation] デングウイルスの血清型流行予測モデルの構築および血清型検出系の確立2019

    • Author(s)
      鶴田爽,  髙橋萌,  町田亮人, 藤田創, 伊藤隼人, 宮本康太郎, 三栖涼雅, 井澤和也, 出口英梨子,  Nattanon Tharachai, 西田 暁史, 安田翔也, 中澤杜浩, 林宜宏, 鈴木亮介, 山村雅幸, 田川陽一
    • Organizer
      第4回デザイン生命工学研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] JCウイルス感染系への応用を目指した神経組織の構築2019

    • Author(s)
      真保恵美子、邱慕、高橋和雅、玉井美保、奴久妻聡一、田川陽一
    • Organizer
      第4回デザイン生命工学研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] GFP-p53導入ES細胞のγ線照射時における細胞性応答2019

    • Author(s)
      小島栞、古賀匠、塚田海馬、玉井美保、松本義久、田川陽一
    • Organizer
      第4回デザイン生命工学研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] マウスES細胞から小腸組織モデルの構築と機能解析2019

    • Author(s)
      岡崎愛加、進藤寛将、玉井美保、田川陽一
    • Organizer
      第4回デザイン生命工学研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 腸管上皮細胞と大腸菌の共培養におけるマイクロ流体デバイスによる菌数制御2019

    • Author(s)
      中澤杜浩、進藤寛将、玉井美保、三宅力、米山恭子、藤山陽一、小関英一、田川陽一
    • Organizer
      第4回デザイン生命工学研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 多元ポリ乳酸足場基材を用いた骨・軟骨モデルの構築2019

    • Author(s)
      川村勇樹、チュウモウチェン、廣江綾香、長岡紀幸、田口精一、田川陽一
    • Organizer
      第4回デザイン生命工学研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 人工転写因子による概日リズムを導入したマウスES細胞由来肝組織モデル2019

    • Author(s)
      QI ZHEN、玉井 美保、今西 未来、山村雅幸、田川 陽一
    • Organizer
      第4回デザイン生命工学研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] INNATE IMMUNE RESPONSES IN MURINE BLASTOCYST IN VITRO MODEL USING EMBRYONIC AND TROPHOBLAST STEM CELLS2018

    • Author(s)
      Takuo Ota, Miho Tamai, Hiroaki Aikawa, and Yoh-ichi Tagawa
    • Organizer
      International Society for Stem Cell Research 2018 Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 宿主-細菌間コミュニケーションの分子生物学的解析のための腸管上皮細胞と大腸菌の共培養系の開発2018

    • Author(s)
      進藤寛将 中澤杜浩 玉井美保 小関英一 藤山陽一 三宅力 米田恭子 金倫基 長谷耕二 田川陽一
    • Organizer
      第41回 日本分子生物学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] I型コラーゲンの分泌およびプロセシング過程の線維芽細胞におけるライブイメージング解析2018

    • Author(s)
      田中利明、常長誠、柳川享世、茂呂忠、内山太郎、上田修、田川陽一、稲垣豊、生駒俊之
    • Organizer
      第50回日本結合組織学会 学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 減少したアミノ酸セットからなるインターフェロンの効率的な進化分子工学2018

    • Author(s)
      保木瑞季、今田貴士、榎本利彦、内山正彦、守矢恒司、一柳光弘、山村雅幸、田川陽一、犬飼直人、鮎川翔太郎、堂前直、鈴木健裕、益田昌子、小原道法、木賀大介
    • Organizer
      第139回日本薬学会年会
    • Related Report
      2018 Research-status Report

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Published: 2018-07-25   Modified: 2021-02-19  

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