| Project/Area Number |
18591932
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Keio University |
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Principal Investigator |
OGAWA Yoko Keio University, School of Medicine, Assistant Professor (30160774)
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| Co-Investigator(Kenkyū-buntansha) |
KUWANA Masataka Keio University, School of Medicine, Associate Professor (50245479)
KAWAKAMI Yutaka Keio University, School of Medicine, Professor (50161287)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| 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)
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| Keywords | Ocular 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 |
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| 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
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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
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