2010 Fiscal Year Final Research Report
Analysis of the onset of ocular chronic graft versus host disease caused by donor-derived fibroblasts and the development of the new therapeutic intervention
| Project/Area Number |
20592058
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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, 医学部, 講師 (30160774)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMMURA Shigeto 慶應義塾大学, 医学部, 准教授 (00235780)
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| Co-Investigator(Renkei-kenkyūsha) |
MATSUZAKI Yumi 慶應義塾大学, 医学部, 准教授 (50338183)
TSUBOTA Kazuo 慶應義塾大学, 医学部, 教授 (40163878)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 眼病理学 / 移植片対宿主病 / ドライアイ / 線維化 / 線維芽細胞 |
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| Research Abstract |
To determine whether donor-derived fibroblasts originate from bone marrow, we used an animal model of chronic graft versus host disease (cGVHD). (Zhang Y, J Immunol, 2002)
To examine the cellular sources of donor-derived fibroblasts in cGVHD recipients, we analyzed mesenchymal stem cells (MSC) (Morikawa S, J Exp Med. 2009) and hematopoietic stem cells (HSC) (Matsuzaki Y, Immunity 2004) from bone marrow. We performed the prospective study using freshly isolated MSCs from donor and HSC from recipient. This is a MSC alone mismatched transplantation. In contrast, MSCs from recipients and HSCs from donor used as a syngeneic MSC transplantation.
In mismatched MSC transplantation, mallory staining of lacrimal gland, liver and salivary gland revealed progressive fibrosis, similar to whole bone marrow transplantation. In contrast, excessive fibrotic areas were scarcely detected 3 and 8 weeks after syngeneic MSC transplantation. When GFP B10.D2 mice were used as donors, GFP+MSCs were found residing in cGVHD fibrotic lesion such as the lacrimal gland, skin and intestine. These results suggest that donor MSCs are partially a source of HSP47+fibroblasts in cGVHD fibrotic tissue. In addition, these results suggest that donor MSCs alone are sufficient to induce cGVHD fibrosis.
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[Journal Article] Topical tranilast for treatment of the early stage of mild dry eye associated with chronic GVHD.2010
Author(s)
Ogawa Y, Dogru M, Uchino M, Tatematsu Y, Kamoi M, Yamamoto Y, Ogawa J, Ishida R, Kaido M, Hara S, R, Matsumoto Y, Kawakita T, Tsubota K.
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Journal Title
Bone Marrow Transplant.(Corresponding author) 45
Pages: 565-569
Peer Reviewed
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[Journal Article] Tear function and lipid layer alterations in dry eye patients with chronic graft-vs-host disease.2009
Author(s)
Ban Y, Ogawa Y, Goto E, Uchino M, Terauchi N, Seki M, Nakaya M, Saiki M, Mori T, Okamoto S, Matsumoto Y. Dogru M, Shimazaki J, Tsubota K.
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Journal Title
Eye.(Corresponding author) 23
Pages: 202-208
Peer Reviewed
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[Remarks] ホームページ等
