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Designing and Developing Innovative Use of Newly Discovered Colonic Epithelial Culture Method Applicable to Clinical Medicine.

Research Project

Project/Area Number 22229005
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

WATANABE Mamoru  東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (10175127)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Tetsuya  東京医科歯科大学, 医歯学総合研究科, 教授 (70265809)
水島 昇  東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (10353434)
Project Period (FY) 2010-05-31 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥216,970,000 (Direct Cost: ¥166,900,000、Indirect Cost: ¥50,070,000)
Fiscal Year 2014: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2013: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2012: ¥32,110,000 (Direct Cost: ¥24,700,000、Indirect Cost: ¥7,410,000)
Fiscal Year 2011: ¥72,670,000 (Direct Cost: ¥55,900,000、Indirect Cost: ¥16,770,000)
Fiscal Year 2010: ¥75,010,000 (Direct Cost: ¥57,700,000、Indirect Cost: ¥17,310,000)
Keywords幹細胞移植 / 再生医療 / 大腸炎創傷治癒 / 大腸上皮 / 組織幹細胞 / 体外培養技術 / 細胞治療 / 大腸炎 / 創傷治癒 / 大腸上皮幹細胞 / 細胞増殖機構 / 細胞分化機構 / 炎症性腸疾患
Outline of Final Research Achievements

It has been expected that the elucidation of the mechanism for the regenerative regulation of intestinal epithelial cells would be applied to the gastrointestinal regenerative medicine.
It has however been technically impossible to assess the normal intestinal epithelial cells ex vivo. In this study, we therefore aimed to assess the function of normal intestinal epithelial cells and to establish the technical basis of clinical application for the primary culture of colonic epithelial cells by developing the long-term, serum-free, 3-dimential culture system of mice normal colon.

Assessment Rating
Verification Result (Rating)

A

Result (Rating)

A+: Progress in the research exceeds the initial goal. More than expected research results are expected.

Report

(8 results)
  • 2015 Research Progress Assessment (Verification Result) ( PDF )
  • 2014 Final Research Report ( PDF )
  • 2013 Annual Research Report   Abstract(Research Progress Assessment) ( PDF )   Research Progress Assessment (Result) ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report

Research Products

(33 results)

All 2014 2013 2012 2011 2010 Other

All Journal Article Presentation Patent(Industrial Property Rights)

  • [Journal Article] Comparison of magnetic resonance and balloon enteroscopic examination of the small intestine in patients with Crohn’s disease.2014

    • Author(s)
      Takenaka K, Ohtsuka K,Watanabe M et al
    • Journal Title

      Gastroenterology.

      Volume: [Epub ahead of print] Pages: 334-342

    • DOI

      10.1053/j.gastro.2014.04.008

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Transplantation of expanded fetal intestinal progenitors contributes to colon regeneration after injury2013

    • Author(s)
      Fordham RP, Yui S, Nakamura T, Watanabe M et. al
    • Journal Title

      Cell Stem Cell

      Volume: 13 Pages: 734-744

    • DOI

      10.1016/j.stem.2013.09.015

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lineage-specific expression of bestrophin-2 and bestrophin-4 in human intestinal epithelial cells2013

    • Author(s)
      Ito G, Okamoto R, Nakamura T, Watanabe M et al
    • Journal Title

      PLoS One.

      Volume: 8

    • DOI

      10.1371/journal.pone.0079693

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Th1/Th17-mediated interstitial pneumonia in chronic colitis mice independent of intestinal microbiota2013

    • Author(s)
      Nemoto Y, Watanabe M et al
    • Journal Title

      J Immunol

      Volume: 190 Pages: 6616-25

    • DOI

      10.4049/jimmunol.1202930

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone marrow-mesenchymal stem cells are a major source of interleukin-7 and sustain colitis by forming the niche for colitogenic CD4 memory T cells2013

    • Author(s)
      Nemoto Y, Nakamura T, Watanabe M et al
    • Journal Title

      Gut

      Volume: 62 Pages: 1142-1152

    • DOI

      10.1136/gutjnl-2012-302029

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The acquisition of malignant potential in colon cancer is regulated by the stabilization of Atonal homolog 1 protein2013

    • Author(s)
      Kano Y
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 432 Pages: 175-181

    • DOI

      10.1016/j.bbrc.2013.01.034

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5(+) stem cell.2012

    • Author(s)
      Yui S, Nakamura T, Sato T, Nemoto Y, Mizutani T, Zheng X, Ichinose S, Nagaishi T, Okamoto R, Tsuchiya K, Clevers H, and Watanabe M
    • Journal Title

      Nat. Med.

      Volume: 18 Pages: 618-23

    • DOI

      10.1038/nm.2695

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The development of colitogenic CD4+ T cells is regulated by IL-7 in collaboration with NK cell function in a murine model of colitis.2012

    • Author(s)
      Yamaji O, Totsuka T
    • Journal Title

      J. Immunol

      Volume: 188 Pages: 2524-2536

    • DOI

      10.4049/jimmunol.1100371

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Real-time analysis of P- gly coprotei n- mediated drug transport across primary intestinal epithelium three-dimensionally cultured in vitro2012

    • Author(s)
      Mizutani T, Nakamura T, et al
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 419 Pages: 238-243

    • DOI

      10.1016/j.bbrc.2012.01.155

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+ stem cell2012

    • Author(s)
      Yui S, Nakamura T, Watanabe M, et al.
    • Journal Title

      Nature Medicine

      Volume: (in press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Luminal CD4+ T cells penetrate gut epithelial monolayers and egress from lamina propria to blood circulation.2012

    • Author(s)
      Nemoto Y, Watanabe M
    • Journal Title

      Gastroenterology.

      Volume: 141 Pages: 2030-2039

    • DOI

      10.1053/j.gastro.2011.08.035

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression ofhath1 gene expression directly regulated by hes1 via notch signaling is associated with goblet cell depletion in ulcerative colitis.2012

    • Author(s)
      Zheng X, Nakamura T, et al
    • Journal Title

      Inflamm Bowel Di

      Volume: 17 Pages: 2251-2260

    • DOI

      10.1002/ibd.21611

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Upregulated IL-7Rα expression on colitogenic memory CD4+ T cells may participate in the development and persistence of chronic colitis2011

    • Author(s)
      Shinohara, T., et al
    • Journal Title

      J Immunol

      Volume: 186 Pages: 2623-2632

    • DOI

      10.4049/jimmunol.1000057

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of hathl gene expression directly regulated by hesl via notch signaling is associated with goblet celldepletion in ulcerative colitis.2011

    • Author(s)
      Zheng X, Nakamura T, Watanabe M, et al.
    • Journal Title

      Inflamm Bowel Dis.

      Volume: in press

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Longitudinal cell formation in the entire human smallintestine is correlated with the localization of Hathl and K1f4.2011

    • Author(s)
      Iwasaki M, Nakamura T, Watanabe M, etal.
    • Journal Title

      J Gastroenterol

      Volume: 46 Pages: 191-202

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Upretulated IL-7 receptor (alpha) expression on colitogenicmemory CD4+ T cells may participate in the developmentand persistence of chronic colitis.2011

    • Author(s)
      Shinohara T, Nakamura T, Watanabe M, etal.
    • Journal Title

      Journal of Immunology

      Volume: 186 Pages: 2623-2632

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Delta-like 1 expression promotes goblet cell differentiation in Notch-inactivated human colonic epithelial cells.2010

    • Author(s)
      Akiyama J, Nakamura T, Watanabe M, et al.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 393 Pages: 662-667

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL-2 is positively involved in the development of colitogenic CD4+ IL-7R alpha high memory T cells inchronic colitis.2010

    • Author(s)
      Kameyama K, Nakamura T, Watanabe M, et al.
    • Journal Title

      Eur J Immunol.

      Volume: 40 Pages: 2423-2436

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cell culture and in-vivo analyses of plaque-derivedcytopathic hepatitis C virus mutants.2010

    • Author(s)
      Mishima K, Nakamura T, Watanabe M, etal.
    • Journal Title

      Virology.

      Volume: 405 Pages: 361-369

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Epithelial regeneration by cultured colonic cells expanded from a single adult Lgr5+ stem cell2012

    • Author(s)
      Nakamura T, Watanabe M
    • Organizer
      The 6th Korea-Japan IBD Symposium
    • Place of Presentation
      Tokyo
    • Year and Date
      2012-01-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] Stem Cells2012

    • Author(s)
      Watanabe M
    • Organizer
      DDW2012
    • Place of Presentation
      San Diego
    • Related Report
      2012 Annual Research Report
  • [Presentation] Real-time analysis of p-glycoprotein-mediated drug transport across primary intestinal epitherial cells three-dimensionally cultured in vitro2012

    • Author(s)
      Mizutani T, Watanabe M et.al.
    • Organizer
      DDW2012
    • Place of Presentation
      San Diego
    • Related Report
      2012 Annual Research Report
  • [Presentation] Regeneration of Damaged Colonic Tissue by Transplantation of Colonic Epithelial Stem Cells Maintained and Expanded In Vitro2011

    • Author(s)
      Yui S, Nakamura T, Watanabe M, et al.
    • Organizer
      DDW2011
    • Place of Presentation
      Chicago
    • Year and Date
      2011-05-07
    • Related Report
      2011 Annual Research Report
  • [Presentation] A long-term, mesenchyme-free in vitro culture system of colonic epithelial cells retaining stem cell compartment with proliferation/differentiation properties.2010

    • Author(s)
      Nakamura T, Watanabe M, et al.
    • Organizer
      Digestive Disease Week 2010
    • Place of Presentation
      New Orleans
    • Related Report
      2010 Annual Research Report
  • [Presentation] A Long-term, fully-defined culture system for colonic epithelial celis that allows efficient expansion of stem cell.2010

    • Author(s)
      Nakamura T, Watanabe M, et al.
    • Organizer
      The 1st JSGE International Topic Conference
    • Place of Presentation
      Kamakura
    • Related Report
      2010 Annual Research Report
  • [Presentation] JGF Marshal & Warren Lecture: Adult tissue stem cell therapy for gastrointestinal diseases.

    • Author(s)
      Watanabe M
    • Organizer
      GASTRO 2013.
    • Place of Presentation
      Shanghai, China
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Colonic Stem Cell Culture and Transplantation-Application in Mucosal Immunology.

    • Author(s)
      Watanabe M
    • Organizer
      ICMI 2013
    • Place of Presentation
      Vancouver, Canada
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Colonic Stem Cell Culture and Transplantation -Application in Mucosal Immunology-.

    • Author(s)
      Watanabe M
    • Organizer
      RCAI-JSI International Symposium.
    • Place of Presentation
      Yokohama, Japan
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Epidemiology of Asian IBD.

    • Author(s)
      Watanabe M
    • Organizer
      1st Annual Meeting of AOCC.
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] State-of-the-Art lecture: Stem cell therapy in IBD?

    • Author(s)
      Watanabe M
    • Organizer
      Falk Sympo 2013
    • Place of Presentation
      Stuttgart, Germany
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Adult Stem Cell Therapy for Gastrointestinal Diseases

    • Author(s)
      Watanabe M
    • Organizer
      International Ulcer Week 2012.
    • Place of Presentation
      Tokyo
    • Related Report
      2012 Annual Research Report
  • [Presentation] Regeneration of damaged colon epithelium by transplanted colon Lgr5+ stem cells maintained and expanded in vitro.

    • Author(s)
      Yui S, Watanabe M et.al.
    • Organizer
      第10回 幹細胞シンポジウム.淡路島
    • Place of Presentation
      Awajishima
    • Related Report
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] 大腸上皮幹細胞の単離・培養技術とこれを用いた大腸上皮移植技術2011

    • Inventor(s)
      渡辺守・中村哲也
    • Industrial Property Rights Holder
      国立大学法人東京医科歯科大学
    • Industrial Property Number
      2011-236469
    • Filing Date
      2011-10-27
    • Related Report
      2011 Annual Research Report

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Published: 2010-08-22   Modified: 2019-07-29  

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