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Role of donorderived fibroblasts in the pathogenic process of lacriimal gland chronic graft-versus-host disease

Research Project

Project/Area Number 18591932
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

OGAWA Yoko  Keio University, School of Medicine, Assistant Professor (30160774)

Co-Investigator(Kenkyū-buntansha) KUWANA Masataka  Keio University, School of Medicine, Associate Professor (50245479)
KAWAKAMI Yutaka  Keio University, School of Medicine, Professor (50161287)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsOcular pathology / Dry eye / Graft-versus-host disease / Hematopietic stem cell transplantation / Immunology / Fibroblast / Fibrosis / Mesenchymal stem cell / 幹細胞 / 慢性移植片対宿主病 / 涙腺 / マーカー / 骨髄
Research Abstract

Tissue atrophy and excessive fibrosis are prominent histologic features of chronic graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation, but the underlying mechanism remains unknown. We investigated whether the fibroblasts increased at the site of pathogenic fibrosis originated from transplanted donor cells in mouse model of chronic GVHD, focusing on lacrimal gland.
In this study, we found the following findings.
1) The disease progression of fibrotic area in cGVHD lacrimal gland was demonstrated.
2) Heat shock protein 47 (HSP47) was found to be an useful marker of fibroblasts in mouse paraffin embedded tissue sections.
3) The chimeric status of accumulated HSP47+ fibroblasts in the lacrimal gland of chronic GVHD mouse model was clearly demonstrated by a series of experiments using lacrimal gland tissue specimens.
4) The primary culture was successfully generated from chronic GVHD lacrimal gland of animal models. There were significant differences be … More tween GVHD lacimal gland and control fibroblasts on the ability of cell proloferation and the morphology.
5) Cellular source of donor-derived fibroblasts might be mesenchymal stem cells, although it was not confirmed.
Since there is no specific treatment proven to be effective for lacrimal gland chronic GVHD at this moment, strategies that inhibit the recruitment of fibroblast precursors into the affected lesion could be a novel therapeutic approach to the fibrotic process in lacrimal gland chronic GVHD.
Our study demonstrates, for the first time, the presence of bone marrow-derived fibroblasts in pathogenic fibrosis of cGVHD lacrimal gland. This finding leads us to propose a hypothesis that bone marrow-derived fibroblasts may contribute to the pathogenesis of fibrotic diseases, such as pulmonary fibrosis, liver cirrhosis, scleroderma, and ocular cicatricial pemphigoid. It would be important to further evaluate the chimeric status on multiple chronic GVHD tissues and potential associations between the chimeric status and response to various therapeutic regimens. Less

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (32 results)

All 2008 2007 2006

All Journal Article (23 results) (of which Peer Reviewed: 11 results) Presentation (7 results) Book (2 results)

  • [Journal Article] Ocular surface and tear functions after topical cyclosporine treatment in dry eye patients with chronic graft-versus-host disease2008

    • Author(s)
      Wang Y, Ogawa Y, et. al.
    • Journal Title

      Bone marrow transplant 41

      Pages: 293-302

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Ocular surface and tear functions after topical cyclosporine treatment in dry eye patients with chronic graft -versus -host disease2008

    • Author(s)
      Ogawa, Y, et. al.
    • Journal Title

      Bone marrow transplant 41

      Pages: 293-302

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Ocular surface and tear functions after topical cyclosporine treatment in dry eye patients with chronic graft-versus-host disease2008

    • Author(s)
      Wang Y^*, Ogawa Y^*, et. al., *^Equally fhst author
    • Journal Title

      Bone marrow transplant 41

      Pages: 293-302

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of heat shock protein 47,a collagen-binding chaperone,in lacrimal gland pathology in patients with cGVHD2007

    • Author(s)
      Oagawa Y, Razzaque MS, et. al.
    • Journal Title

      Invest Ophthalmol Vis Sci 48

      Pages: 1079-1086

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Spontaneous lacrimal punctal occlusion associated with ocular chronic graft-versus-host disease2007

    • Author(s)
      Kamoi M, Ogawa Y*, et. al.
    • Journal Title

      Cur Eye Res 32

      Pages: 837-842

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Inflammatory myopathy with anti-Golgi antibody and anti-SS-A/Ro antibody2007

    • Author(s)
      Hattori H, Ogawa Y, et. al.
    • Journal Title

      Internal Medicine 46

      Pages: 1927-1930

    • NAID

      130000078608

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Beta-catenin activation and epithelial-mesenchymal transition in the pathogenesis of pterygium2007

    • Author(s)
      Kato N, Shimmura S, Ogawa Y, et. al.
    • Journal Title

      Invest phthalmol Vis Sci 48

      Pages: 1511-1517

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Noninvasive interference tear meniscometry in dry eye patients with Sjogren's syndrome2007

    • Author(s)
      Ogawa Y, Tsubota K, et. al.
    • Journal Title

      Am J Ophthalmol 144

      Pages: 232-237

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The impact of nasal conjunctival chalasis on tear functions and ocular surface findings2007

    • Author(s)
      Ogawa Y, Shimazaki J, et. al.
    • Journal Title

      Am J Ophthalmol 144

      Pages: 930-937

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Research in dry eye:report of the Research Subcommittee of the International Dry Eye Work Shop(2007)2007

    • Author(s)
      Ogawa Y, et. al.
    • Journal Title

      Ocul Surf 5

      Pages: 179-193

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Ocular complications in a child with acute graft-versus-host disease following cord blood stem cell transplantation:therapeutic challenges.2007

    • Author(s)
      Uchino M, Ogawa Y, et. al.
    • Journal Title

      Acta Ophthalmol Scand 84

      Pages: 545-548

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Role of heat shock protein 47, a collagen-binding chaperone, in lacrimal gland pathology in patients with cGVHD2007

    • Author(s)
      Ogawa, Y, Kawakami, Y, Kuwana, M., et. al.
    • Journal Title

      Invest Ophthalmol Vis Sci 48

      Pages: 1079-1086

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Spontaneous lacrimal punctal occlusion associated with ocular chronic graft-versus-host disease2007

    • Author(s)
      Ogawa, Y, et. al., Mori, T, Okamoto, S, Shimazaki, J, Tsubota, K
    • Journal Title

      Cur Eye Res 32

      Pages: 837-842

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Inflammatory myopathy with anti-Golgi antibody and anti-SS-A/Ro antibody2007

    • Author(s)
      Ogawa, Y, et. al.
    • Journal Title

      Internal Medicine 46

      Pages: 1927-1930

    • NAID

      130000078608

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Beta-catenin activation and epithelial-mesenchymal transition in the pathogenesis of pterygium2007

    • Author(s)
      Ogawa, Y, et. al.
    • Journal Title

      Invest phthalmol Vis Sci 48

      Pages: 1511-1517

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Noninvasive interference tear meniscometry i n dry eye patients with Sjogren's syndrome2007

    • Author(s)
      Ogawa, Y, et. al.
    • Journal Title

      Am J Ophthalmol 144

      Pages: 232-237

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The impact of nasal conjunctival chalasis on tear functions and ocular surface findings2007

    • Author(s)
      Ogawa, Y, et. al.
    • Journal Title

      IAm J Ophthalmol 144

      Pages: 930-937

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Research in dry eye : Report of the Research Subcommittee of the International Dry Eye Work Shop (2007)2007

    • Author(s)
      Ogawa, Y, et. al.
    • Journal Title

      Ocul Surf 5

      Pages: 179-193

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Spontaneous lacrimal punctal occlusion associated with ocular chronic graft-versus-host disease2007

    • Author(s)
      Kamoi M, Ogawa Y^*, et. al., *^Corresonding author
    • Journal Title

      Cur Eye Res. 32

      Pages: 837-842

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The impact of nasal conjunctival chalasis on tear functions and ocular surface finding2007

    • Author(s)
      Wang Y, Ogawa Y, et. al.
    • Journal Title

      Am J Ophthalmol 144

      Pages: 930-937

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of heat shock protein 47, a collagen-binding chaperone, in lacrimal gland pathology in patients with cGVHD2007

    • Author(s)
      Ogawa Y, Razzaque MS, Kameyama K, Hasegawa G, Shimmura S, Kawai M, Okamoto S, Ikeda Y, Tsubota K, Kawakami Y, Kuwana
    • Journal Title

      Invest Ophthalmol Vis Sci 48.3

      Pages: 1079-1086

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Ocular complications in a child with acute graft-versus-host disease following cord blood stem cell transplantation : therapeutic challenges2006

    • Author(s)
      Ogawa, Y, et. al.
    • Journal Title

      Acta Ophthalmol Scand 84

      Pages: 545-548

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Ocular complications in a child with acute graft-versus-host disease following cord blood stem cell transplanation : therapeutic challenges2006

    • Author(s)
      Uchino M, Ogawa Y, Kawai M, Shimada H, Kameyama K, Okamoto S, Dogru M, Tsubota K.
    • Journal Title

      Acta Ophthalmol Scand 84.4

      Pages: 545-548

    • Related Report
      2006 Annual Research Report
  • [Presentation] Collagen Secretion From HSP 47-Expressing Conjunctival Basal Epithelia in Dry Eye Associated With Chronic Graft versus Host Disease2007

    • Author(s)
      Yoko Ogawa, et. al.
    • Organizer
      The Association for Research in Vision and Ophthalmology 2007(ARVO2007)
    • Place of Presentation
      Fort Lauderdale,USA
    • Year and Date
      2007-05-10
    • Related Report
      2007 Annual Research Report
  • [Presentation] Collagen Secretion From HSP 47-Expressing Conjunctival Basal Epithelia in Dry Eye Associated With Chronic Graft versus Host Disease2007

    • Author(s)
      Y.Ogawa, S.Shimmura, et. al.
    • Organizer
      The Association for Research in Vision and Ophtha Imology 2007(ARV02007)
    • Place of Presentation
      Fort Lauderdale,Florida,USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Collagen secretion from HSP 47-expressing lacrimal gland myoepithelia in dry eye associated with chronic graft versus host disease2007

    • Author(s)
      Y Ogawa, MS.Razzaque, et. al.
    • Organizer
      5th International Conference on the Tear Film&Ocular Surface:Basic Science and Clinical Relevance
    • Place of Presentation
      Taormina,Sicily,Italy
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Collagen Secretion From HSP 47-Expressing Conjunctival Basal Epithelia in Dry Eye Associated With Chronic Graft versus2007

    • Author(s)
      Y., Ogawa, S., Shimmura, et. al.
    • Organizer
      The Association for Research in Vision and Ophthalmology 2007 (ARV02007)
    • Place of Presentation
      Fort Lauderdale, Florida, USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Collagen secretion from HSP 47-expressing lacrimal gland myoepithelia in dry eye associated with chronic graft versus host disease2007

    • Author(s)
      Y, Ogawa, MS., Razzaque, et. al.
    • Organizer
      5th International Conference on the Tear Film & Ocular Surface : Basic Science and Clinical Relevance
    • Place of Presentation
      Taormina, Sicily, Italy
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Pathogenic fibrosis and inflammation of conjunctival chronic graft versus host disease2006

    • Author(s)
      Y.Ogawa, K.Yamazaki, et. al.
    • Organizer
      The Association for Research in Vision and Ophtha Imology 2006(ARV02006)
    • Place of Presentation
      Fort Lauderdale,Florida,USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Pathogenic fibrosis and inflammation of conjunctival chronic graft versus host disease2006

    • Author(s)
      Y., Ogawa, K., Yamazaki, et. al.
    • Organizer
      The Association for Research in Vision and Ophthalmology 2006 (ARV02006)
    • Place of Presentation
      Fort Lauderdale, Florida, USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Text眼科学2007

    • Author(s)
      小川 葉子, 他
    • Total Pages
      15
    • Publisher
      南山堂
    • Related Report
      2007 Annual Research Report
  • [Book] シェーグレン症候群vs cGVHD 眼科プラティス8 いますぐ役立つ眼病理 石橋達郎編2006

    • Author(s)
      小川葉子
    • Publisher
      文光堂
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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