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Identification of gastrointestinal epithelial stem cell and development of regeneration therapy for IBD

Research Project

Project/Area Number 14370192
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKeio University

Principal Investigator

HIBI Toshifumi  Keio University, School of Medicine, Professor, 医学部, 教授 (50129623)

Co-Investigator(Kenkyū-buntansha) WATANABE Mamoru  Tokyo Medical & Dental University, Dept of Medicine, Professor, 医学部, 教授 (10175127)
OKANO Hideyuki  Keio University, School of Medicine, Professor, 医学部, 教授 (60160694)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2003: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 2002: ¥7,900,000 (Direct Cost: ¥7,900,000)
Keywordsintestinal epithelial cell / stem cell / side population cell / musashi-1 / inflammatory bowel disease / regeneration of mucosa
Research Abstract

Epithelial renewal occurs in the crypts through a coordinated series of events involving proliferation, differentiation and migration toward the intestinal lumen. It was believed that pluripotent stem cells were located at the lower third of the crypt and generated differentiated cells, such as intestinal epithelial cells, enteroendocrine cells, paneth cells and goblet cells. However, their manner of proliferation and differentiation remains unknown because they lack specific markers and methods of purification and culture. In this study, we propose a new technique to enrich epithelial stem cells and evaluate their phenotype.
We have separated crypts and villi from adult murine small intestine, and have shown that dephosphorylated β catenin and musashi-1 was enriched in crypts fraction. Crypt epithelial cells contained increased numbers of side population (SP) cells and as compared with villous epithelial cells. In adult intestinal epithelial cells, SP cells have higher amounts of ABCG-2 as compared with main population (MP) cells. Fetal intestinal epithelial cells contained large numbers of SP cells. Dephosphorylated β catenin was enriched in SP cells as compared with MP cells.
These results suggested that intestinal stem cell could be purified using SP cell fraction in intestinal epithelial cells. Further study is needed to determine whether SP cells have functional stem cell activities in vivo and in vitro.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Matsuzaki Y, et al.: "Unexpectedly efficient homing capacity of purified murine hematopoietic stem cells."Immunity. 20(1). 87-93 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato T, et al.: "Hyperexpression of Inducible Costimulator and Its Contribution on Lamina Propria T cells in Inflammatory Bowel Disease."Gastroenterology. 126(3). 829-839 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamazaki M, et al.: "Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis."J Immunol. 171(3). 1556-1563 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ezaki T, et al.: "A specific genetic alteration on chromosome 6 in ulcerative colitis-associated colorectal cancers."Cancer Res. 63(13). 3747-3749 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okamoto R, et al.: "Damaged epithelia regenerated by bone marrow-derived cells in the human Gastrointestinal tract."Nature Med. 8(9). 1011-1017 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsuzaki Y, Kinjo K, Mulligan RC, Okano H: "Unexpectedly efficient homing capacity of purified murine hematopoietic stem cell."Immunity. 20. 87-93 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sato T, Kanai T, Watanabe M, Sakuraba A, Okamoto S, Nakai T, Okazawa A, Inoue N, Totsuka T, Yamazaki M, Kroczek RA, Fukushima T, Ishii H, Hibi T: "Hyperexpression of Inducible Costimulator and Its Contribution on Lamina Propria T cells in Inflammatory Bowel Disease."Gastroenterology. 126. 829-839 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamazaki M, Yajima T, Tanabe M, Fukui K, Okada E, Okamoto R, Oshima S, Nakamura T, Kanai T, Uehira M, Takeuchi T, Ishikawa H, Hibi T, Watanabe M: "Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis."J Immunol. 171. 1556-1563 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ezaki T, Watanabe M, Inoue N, Kanai T, Ogata H, Iwao Y, Ishii H, Hibi T: "A specific genetic alteration on chromosome 6 in ulcerative colitis-associated colorectal cancers."Cancer Res. 63. 3747-3749 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okamoto R, Yajima T, Yamazaki M, Kanai T, Mukai M, Okamoto S, Ikeda Y, Hibi T, Inazawa J, Watanabe M: "Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract."Nature Med. 8(9). 1011-1017 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsuzaki Y, et al.: "Unexpectedly efficient homing capacity of purified murine hematopoietic stem cells."Immunity. 20(1). 87-93 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sato T, et al.: "Hyperexpression of Inducible Costimulator and Its Contribution on Lamina Propria T cells in Inflammatory Bowel Disease."Gastroenterology. 126(3). 829-839 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamazaki M, et al.: "Mucosal T cells expressing high levels of IL-7 receptor are potential targets for treatment of chronic colitis."J Immunol. 171(3). 1556-1563 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ezaki T, et al.: "A specific genetic alteration on chromosome 6 in ulcerative colitis-associated colorectal cancers."Cancer Res. 63(13). 3747-3749 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kokuzawa J, et al.: "Hepatocyte growth factor promotes proliferation and neuronal differentiation of neural stem cells from mouse embryos."Mol Cell Neurosci. 24(1). 190-197 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Potten CS, et al.: "Identification of a putative intestinal stem cell marker and early lineage marker ; Musashi1."Differentiation. 71(1). 28-41 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Potten CS, et al.: "Identification of a putative intestinal stem cell marker and early lineage marker; Musashi1"Differentiation. 71(1). 28-41 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kayahara T, et al.: "Candidate markers for stem and early progenitor cells, Musashi-1 and Hes1, are expressed in crypt base columnar cells of mouse small intestine"FEBS Lett. 535(1-3). 131-135 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okano H, et al.: "Musashi: a translational regulator of cell fate"J Cell Sci. 115(7). 1355-1359 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okamoto R, et al.: "Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract"Nature Med. 8(9). 1011-1017 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Naganuma M, et al.: "Characterization of structures with T-Lymphocyte aggregates in ileal villi of Crohn's disease"Am J Gastroenterol. 97(7). 1741-1747 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kobayashi K, et al.: "Distribution and partial characterisation of lgG Fc binding protein in various mucin producing cells and body fluids"Gut. 51(2). 169-176 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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