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Establishment of enterohormone farm by using cultured human intestinal epithelial cells

Research Project

Project/Area Number 15K15286
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Okamoto Ryuichi  東京医科歯科大学, 再生医療研究センター, 教授 (50451935)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords腸上皮 / 消化管ホルモン / 腸上皮オルガノイド
Outline of Final Research Achievements

In this study, we investigated the method to induce secretory-lineage differentiation of cultured human intestinal organoids, and also performed some functional analyses of those organoids. Consequently, we successfully established over 40-lines of human small intestinal- or colonic-organoids from endoscopic biopsy specimens. Short-term exposure to a gamma-secretase inhibitor, combined with depletion of Wnt3a, SB20190 and Nicotinamide, certainly directed human intestinal organoids towards secretory cell-lineage differentiation. We also established a quantitative analysis system to evaluate the response of human intestinal organoids to a secretagogue, PGE2, or an enterohormone, VIP, and showed their properties to regulate the body-fluid balance.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (14 results)

All 2016 2015

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 8 results)

  • [Journal Article] PGE2 is a direct and robust mediator of anion/fluid secretion by human intestinal epithelial cells.2016

    • Author(s)
      Fujii S, Okamoto R, Suzuki K, Kawamoto A, Ishibashi F, Nakata T, Murano T, Ito G, Shimizu H, Mizutani T, Oshima S, Tsuchiya K, Nakamura T, Araki A, Ohtsuka K, Watanabe M
    • Journal Title

      Sci. Rep.

      Volume: 6 Issue: 1 Pages: 36795-36795

    • DOI

      10.1038/srep36795

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Role of epithelial cells in the pathogenesis and treatment of inflammatory bowel disease.2016

    • Author(s)
      Ryuichi Okamoto, Mamoru Watanabe
    • Journal Title

      J. Gastroenterol

      Volume: 51 Issue: 1 Pages: 11-21

    • DOI

      10.1007/s00535-015-1098-4

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reduced human α-defensin 6 in non-inflamed jejunal tissue of Crohn’s disease patients2016

    • Author(s)
      Hayashi R , Tsuchiya K, Okamoto R,Watanabe M,et al
    • Journal Title

      Inflammatory Bowel Diseases

      Volume: 22 Issue: 5 Pages: 1119-28

    • DOI

      10.1097/mib.0000000000000707

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Perspectives for Regenerative Medicine in the Treatment of Inflammatory Bowel Diseases.2015

    • Author(s)
      Ryuichi Okamoto, Mamoru Watanabe
    • Journal Title

      Digestion

      Volume: 92 Issue: 2 Pages: 73-77

    • DOI

      10.1159/000438663

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] TNFAIP3 promotes survival of CD4 T cells by restricting MTOR and promoting autophagy.2015

    • Author(s)
      Matsuzawa Y, Oshima S, Takahara M, Maeyashiki C, Nemoto Y, Kobayashi M, Nibe Y, Nozaki K, Nagaishi T, Okamoto R, Tsuchiya K, Nakamura T, Averil Ma, Watanabe M
    • Journal Title

      Autophagy

      Volume: 11 Issue: 7 Pages: 1052-1062

    • DOI

      10.1080/15548627.2015.1055439

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Atonal homolog 1 protein stabilized by tumor necrosis factor α induces high malignant potential in colon cancer cell line.2015

    • Author(s)
      Keita Fukushima, Kiichiro Tsuchiya,Okamoto Ryuichi, Mamoru Watanabe,et al
    • Journal Title

      Cancer Sci

      Volume: 106 Issue: 8 Pages: 1000-7

    • DOI

      10.1111/cas.12703

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] In vitro organoid model reveals PGE2 as a robust mediator of chloride & water secretion by human intestinal epithelial cells2016

    • Author(s)
      Satoru Fujii, Kohei Suzuki, Ami Kawamoto, Fumiaki Ishibashi, Toru Nakata, Go Ito, Hiromichi Shimizu, Tomohiro Mizutani, Kiichiro Tsuchiya, Tetsuya Nakamura, Kazuo Ohtsuka, Ryuichi Okamoto, Mamoru Watanabe
    • Organizer
      DDW2016
    • Place of Presentation
      サンディエゴ(米国)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Establishment of a 3D cell culture-based screening platform to identify natural products that can regulate transepithelial water transport of the human gastrointestinal tract.2015

    • Author(s)
      Satoru Fujii, Ryuichi Okamoto, Toru Nakata, Kohei Suzuki, Fumiaki Ishibashi, Ami Kawamoto,Sayaka Ohashi Segawa, Tomohiro Mizutani, Kiichiro Tsuchiya, Tetsuya Nakamura, Mamoru Watanabe.
    • Organizer
      Pacifichem2015
    • Place of Presentation
      ハワイ(米国)
    • Year and Date
      2015-12-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Contiuous stimulation with cytokines leads to irreversible activation of NF-γb signaling in colonic epithelial cells by organoid culture.2015

    • Author(s)
      Shuji Hibiya, Kiichiro Tsuchiya, Tomoaki Shirasaki, Keita Fukushima, Ryohei Hayashi, Nobukatsu Horita, Shigeru Oshima ,Ryuichi Okamoto, Tetsuya Nakamura,Mamoru Watanabe
    • Organizer
      UEGW2015
    • Place of Presentation
      バルセロナ(スペイン)
    • Year and Date
      2015-10-27
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] A novel fluorescent labelling system into small intestinal organoid reveals independent long-lived intestinal stem cells in a crypt.2015

    • Author(s)
      Horita N,Tsuchiya K,Hayashi R,Fukushima K,Hibiya S,Fukuda M,Mizutani T,Okamoto R,Nakamura T and Watanabe M.
    • Organizer
      AOCC2015
    • Place of Presentation
      北京(中国)
    • Year and Date
      2015-06-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Enrichment of Intestinal Stem Cells by the 3D-Culture of IBD Patient Derived Intestinal epithelium.2015

    • Author(s)
      Kohei Suzuki,Satoru Fujii,Toru Nakata,Ami Kawamoto,Fumiaki Ishibashi,Sayaka Ohashi Segawa, Tomohiro Mizutani, Kiichiro Tsuchiya,Kazuo Otsuka,Tetsuya Nakamura,Ryuichi Okamoto,Mamoru Watanabe.
    • Organizer
      AOCC2015
    • Place of Presentation
      北京(中国)
    • Year and Date
      2015-06-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Continuous Stimulation With Cytokines Leads to Irreversible Accumulation of NF-kB Signaling in Colonic Epithelial Cells.2015

    • Author(s)
      Shuji Hibiya, Kiichiro Tsuchiya, Keita Fukushima, Ryohei Hayashi, Nobukatsu Horita, Shigeru Oshima, Ryuichi Okamoto, Tetsuya Nakamura, Mamoru Watanabe.
    • Organizer
      DDW 2015
    • Place of Presentation
      ワシントン(米国)
    • Year and Date
      2015-05-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Distinct Role of Notch Ligands, DLL1 and Dll4, in Normal and in Tumor Intestinal Epithelium.2015

    • Author(s)
      Toru Nakata, Hiromichi Shimizu, Kohei Suzuki, Satoru Fujii, Go Ito, Kiichiro Tsuchiya, Tetsuya Nakamura, Ryuichi Okamoto, Katsuto Hozumi, Mamoru Watanabe.
    • Organizer
      DDW 2015
    • Place of Presentation
      ワシントン(米国)
    • Year and Date
      2015-05-19
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Notch Ligands DLL1 and Dll4 Are Expressed by Distinct Population of Epithelial Cells in the Mice Intestine.2015

    • Author(s)
      Hiromichi Shimizu, Kohei Suzuki, Satoru Fujii, Toru Nakata, Go Ito, Tatsuro Murano, Kiichiro Tsuchiya, Tetsuya Nakamura, Ryuichi Okamoto, Katsuto Hozumi, Mamoru Watanabe.
    • Organizer
      DDW 2015
    • Place of Presentation
      ワシントン(米国)
    • Year and Date
      2015-05-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2018-10-01  

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