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Development of hybrid intestine system and its applications

Research Project

Project/Area Number 17K19674
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Organ-based internal medicine and related fields
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Nakamura Tetsuya  東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座教授 (70265809)

Co-Investigator(Kenkyū-buntansha) 松岡 克善  東京医科歯科大学, 大学院医歯学総合研究科, 寄附講座准教授 (40307393)
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords腸オルガノイド / 3次元培養 / 再生医療 / 移植・再生医療 / 再生医学 / 生理学 / 細胞・組織 / 外科
Outline of Final Research Achievements

My research group first described that mouse colonic epithelial organoids can regenerate colonic epithelia when transplanted. By extending this study, we have shown that various types of intestinal epithelial organoids, such as those derived from fetal and adult mouse small intestines, can regenerate the intestinal epithelium in vivo. In this research proposal we have further shown the methodology of open abdominal surgery to replace epithelial tissues of various parts of the mouse colon with epithelial organoids obtained from different parts of intestines. By employing this, we have been able to investigate the changes in gene expression patterns and the histology of ectopically-grafted intestinal epithelial cells, which may provide valuable insights into how intestinal epithelia preserve their lineage-specific characteristics throughout isolation, organoid culture and grafting processes.

Academic Significance and Societal Importance of the Research Achievements

大腸上皮を異なる上皮組織に置換する本研究の試みは、元来均一である組織内に周囲と異なる組織を生着させ機能させる技術開発として先進性がある。また、小腸の物理的欠損で引き起こされる小腸機能不全に対し、大腸機能を改変し治療する新しい再生医療コンセプトにつながる点で重要である。今後は、大腸の一部にたとえばある種のホルモン産生機能を付加するなど、全く新しい医療技術開発につながる可能性を秘めた有意義な研究であったと考える。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (13 results)

All 2019 2018 2017

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (4 results) (of which Invited: 3 results)

  • [Journal Article] B cell activation in the cecal patches during the development of an experimental colitis model.2018

    • Author(s)
      Taro Watabe, Takashi Nagaishi, Naoya Tsugawa, Yudai Kojima, Nisha Jose, Akinori Hosoya, Michio Onizawa, Yasuhiro Nemoto, Shigeru Oshima, Tetsuya Nakamura, Hajime Karasuyama, Takahiro Adachi, Mamoru Watanabe
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 496 Issue: 2 Pages: 367-373

    • DOI

      10.1016/j.bbrc.2018.01.053

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single cell analysis of Crohn’s disease patient-derived small intestinal organoids reveals disease activity-dependent modification of stem cell properties2018

    • Author(s)
      Suzuki Kohei、Murano Tatsuro、Shimizu Hiromichi、Ito Go、Nakata Toru、Fujii Satoru、Ishibashi Fumiaki、Kawamoto Ami、Anzai Sho、Kuno Reiko、Kuwabara Konomi、Takahashi Junichi、Tsuchiya Kiichiro、Nakamura Tetsuya、Ohtsuka Kazuo、Watanabe Mamoru、Okamoto Ryuichi
    • Journal Title

      Journal of Gastroenterology

      Volume: 印刷中 Issue: 9 Pages: 1035-1047

    • DOI

      10.1007/s00535-018-1437-3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recent progress in organoid culture to model intestinal epithelial barrier functions2018

    • Author(s)
      Nakamura Tetsuya
    • Journal Title

      International Immunology

      Volume: 31 Issue: 1 Pages: 13-21

    • DOI

      10.1093/intimm/dxy065

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ubiquitin D is Upregulated by Synergy of Notch Signalling and TNF-α in the Inflamed Intestinal Epithelia of IBD Patients2018

    • Author(s)
      Kawamoto Ami、Nagata Sayaka、Anzai Sho、Takahashi Junichi、Kawai Mao、Hama Minami、Nogawa Daichi、Yamamoto Kouhei、Kuno Reiko、Suzuki Kohei、Shimizu Hiromichi、Hiraguri Yui、Yui Shiro、Oshima Shigeru、Tsuchiya Kiichiro、Nakamura Tetsuya、Ohtsuka Kazuo、Kitagawa Masanobu、Okamoto Ryuichi、Watanabe Mamoru
    • Journal Title

      Journal of Crohn's and Colitis

      Volume: 13 Issue: 4 Pages: 495-509

    • DOI

      10.1093/ecco-jcc/jjy180

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Advancing Intestinal Organoid Technology Toward Regenerative?Medicine2018

    • Author(s)
      Nakamura Tetsuya、Sato Toshiro
    • Journal Title

      Cellular and Molecular Gastroenterology and Hepatology

      Volume: 5 Issue: 1 Pages: 51-60

    • DOI

      10.1016/j.jcmgh.2017.10.006

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Contribution of ATOH1 + Cells to the Homeostasis, Repair, and Tumorigenesis of the Colonic Epithelium2018

    • Author(s)
      Ishibashi Fumiaki、Shimizu Hiromichi、Nakata Toru、Fujii Satoru、Suzuki Kohei、Kawamoto Ami、Anzai Sho、Kuno Reiko、Nagata Sayaka、Ito Go、Murano Tatsuro、Mizutani Tomohiro、Oshima Shigeru、Tsuchiya Kiichiro、Nakamura Tetsuya、Watanabe Mamoru、Okamoto Ryuichi
    • Journal Title

      Stem Cell Reports

      Volume: 10 Issue: 1 Pages: 27-42

    • DOI

      10.1016/j.stemcr.2017.11.006

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] YAP/TAZ-Dependent Reprogramming of Colonic Epithelium Links ECM Remodeling to Tissue Regeneration2018

    • Author(s)
      Yui S、Azzolin L、Maimets M、Pedersen MT、Fordham RP、Hansen SL、Larsen HL、Guiu Jordi、Alves MRP、Rundsten CF、Johansen JV、Li Y、Madsen CD、Nakamura T、Watanabe M、Nielsen OH、Schweiger PJ、Piccolo S、Jensen KB
    • Journal Title

      Cell Stem Cell

      Volume: 22 Issue: 1 Pages: 35-49

    • DOI

      10.1016/j.stem.2017.11.001

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reconstruction of the Human Colon Epithelium In Vivo.2018

    • Author(s)
      Sugimoto S, Ohta Y, Fujii M, Matano M, Shimokawa M, Nanki K, Date S, Nishikori S, Nakazato Y, Nakamura T, Kanai T, Sato T.
    • Journal Title

      Cell Stem Cell.

      Volume: 22 Issue: 2 Pages: 171-176

    • DOI

      10.1016/j.stem.2017.11.012

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distinct intestinal adaptation for vitamin B12 and bile acid absorption revealed in a new mouse model of massive ileocecal resection.2017

    • Author(s)
      Matsumoto Y, Mochizuki W, Akiyama S, Matsumoto T, Nozaki K, Watanabe M, Nakamura T
    • Journal Title

      Biol Open.

      Volume: 15 Pages: 1364-1374

    • DOI

      10.1242/bio.024927

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] オルガノイド移植による未来の腸再生医療2019

    • Author(s)
      中村哲也
    • Organizer
      第31回小腸移植研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 腸オルガノイドによる再生医療を目指した新規小腸機能不全マウスモデルの開発と移植方法の検討2018

    • Author(s)
      松本有加、渡辺守、中村哲也
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Intestinal Stem Cell Transplantation2017

    • Author(s)
      中村哲也
    • Organizer
      第54回日本消化器免疫学会総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] オルガノイド移植による腸再生医療2017

    • Author(s)
      中村哲也
    • Organizer
      第33回日本小児外科学会・秋季シンポジウム
    • Related Report
      2017 Research-status Report
    • Invited

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Published: 2017-07-21   Modified: 2020-03-30  

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