2013 Fiscal Year Final Research Report
Focus on mechanism of chronic ocular graft-vessus-host disease caused by donor-derived mesenchymal stem cells toward development of new treatment.
| Project/Area Number |
23592590
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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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 慶應義塾大学, 医学部, 特任准教授 (30160774)
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| Co-Investigator(Renkei-kenkyūsha) |
TUBOTA Kazuo 慶應義塾大学, 医学部, 教授 (40163878)
SHIMMURA Shigeto 慶應義塾大学, 医学部, 准教授 (00235780)
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| Project Period (FY) |
2011 – 2013
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| Keywords | ドライアイ / 線維化 / 免疫応答 / 造血幹細胞移植 / T細胞 / 間葉系幹細胞 |
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| Research Abstract |
Chronic ocular graft-versus-host disease(GVHD), i.e. chronic GVHD related dry eye, is a major complication after allogeneic hematopoietic stem cell transplantation. We have found that donor-derived mesenchymal stem cells play a significant role for underlying mechanism of chronic ocular GVHD fibrosis. We have found donor MSCs engrafted GVHD target organs such as lacrimal gland, conjunctiva, salivary gland, lung, skin, liver and intestine. We also suggested that donor MSCs interacted with T cells in the pathogenic regions and contributed to the onset of cGVHD and chronicity of this disease. We further showed donor MSCs increased IL-6 leading to decreased Tregs and conversely an increase in Th 17 cells in peripheral blood. Our results show that donor MSCs trigger immune responses in T cells and immune mediated fibrosis of chronic ocular GVHD.
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Research Products
(34 results)
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[Journal Article] Angiotensin II type 1 receptor antagonist attenuates lacrimal gland, lung, and liver fibrosis in a murine model of chronic graft-versus-host disease2013
Author(s)
Yaguchi S, Ogawa Y, Shimmura S, Kawakita T, Hatou S, Satofuka S, Nakamura S, Imada T, Miyashita H, Yoshida S, Yaguchi T, Ozawa Y, Mori T, Okamoto S, Kawakami Y, Ishida S, Tsubota K
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Journal Title
PLoS ONE
Volume: 8(6)
Pages: e64724
DOI
Peer Reviewed
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[Journal Article] Validation of different sets of criteria for the diagnosis of Sjögren's syndrome in Japanese patients2013
Author(s)
Tsuboi H, Hagiwara S, Asashima H, Umehara H, Kawakami A, Nakamura H, Sano H, Tsubota K, Ogawa Y, Takamura E, Saito I, Inoue H, Nakamura S, Moriyama M, Takeuchi T, Tanaka Y, Hirata S, Mimori T, Matsumoto I, Sumida T
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Journal Title
Mod Rheumatol
Volume: 23(2)
Pages: 219-25
DOI
Peer Reviewed
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[Journal Article] Accumulation of secretory vesicles lacrimal gland epithelia is related to non-Sjögren's type dry eye in visual display terminal users2012
Author(s)
Kamoi M, Ogawa Y, Nakamura S, Dogru M, Nagai T, Obata H, Ito M, Kaido M, Kawakita T, Okada Y, Kawakami Y, Shimmura S, Tsubota K
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Journal Title
PLoS One
Volume: 7(9)
Pages: e43688
DOI
Peer Reviewed
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[Journal Article] Presence and physiologic function of the Renin-Angiotensin System in mouse lacrimal gland2012
Author(s)
Yaguchi S, Ogawa Y, Shimmura S, Hatou S, Nakamura S, Inaba T, Imada T, Ozawa Y, Kawakami Y, Ishida S, Tsubota K
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Journal Title
Invest Ophthalmol Vis Sci
Volume: 53(9)
Pages: 5416-5425
DOI
Peer Reviewed
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[Journal Article] Age-related dysfunction of the lacrimal gland and oxidative stress : evidence from the Cu,Zn-superoxide dismutase-1 (Sod1) knockout mice2012
Author(s)
Kojima T, Wakamastu TH, Dogru M, Ogawa Y, Igarashi A, Ibrahim OM, Inaba T, Shimizu T, Noda S, Obata H, Nakamura S, Wakamatsu A, Shirasawa T, Shimazaki J, Negishi K, Tsubota K
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Journal Title
Am J Pathol
Volume: 180(5)
Pages: 1879-1896
DOI
Peer Reviewed
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[Journal Article] Mucosal microvilli in dry eye patients with chronic GVHD2012
Author(s)
Tatematsu Y, Ogawa Y, Shimmura S, Dogru M, Yaguchi S, Nagai T, Yamazaki K, Kameyama K, Okamoto S, Kawakami Y, Tsubota K
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Journal Title
Bone Marrow Transplant
Volume: 47(3)
Pages: 416-425
DOI
Peer Reviewed
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[Presentation] Donor mesenchymal stem cells induce immune response in lacrimal gland chronic graft versus host disease in an animal model2013
Author(s)
Ogawa Y, Shimmura S, Morikawa S, Mabuchi Y, Sato Y, Suzuki S, Yaguchi T, Inaba, T, Yaguchi S, Okamoto S, Kawakami Y, Okano H, Maztsuzaki Y, Tsubota K
Organizer
The 12th International Symposium on Sjögren's Syndrome
Place of Presentation
Kyoto , Japan
Year and Date
20131009-12
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[Presentation] Interaction between donor mesenchymal stem cells and recipient-derived T cells in the pathogenesis of ocular chronic graft versus host disease2012
Author(s)
Ogawa Y, Shimmura S, Morikawa S, Yaguchi T, Yaguchi S, Inaba T, Kawakami Y, Okano H, Matsuzaki Y, Tsubota K
Organizer
The association for research in vision and ophthalmology 2012 (ARVO 2012) Annual Meeting
Place of Presentation
Fort Lauderdale, Florida, USA
Year and Date
20120506-10
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[Presentation] A role of recipient-derived T cells in ocular chronic graft-versus-host disease2012
Author(s)
Ogawa Y, Shimmura S, Morikawa S, Mabuchi Y, Yaguchi Y, Inaba T, Kawakami Y, Okano H, Matsuzaki Y, Tsubota K
Organizer
1st Conference on the Tear Film and Ocular Surface in Asia
Place of Presentation
Kanagawa, Japan
Year and Date
20120402-04
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[Presentation] Donor mesenchymal stem cells trigger chronic graft-versus-host disease following minor antigen-mismatched bone marrow transplantation2011
Author(s)
Ogawa Y, Shimmura S, Morikawa S, Mabuchi Y, Yaguchi T, Inaba T, Yaguchi S, Kawakami Y, Okano H, Tsubota K, Matsuzaki Y
Organizer
第40回日本免疫学会総会
Place of Presentation
千葉
Year and Date
2011-11-28
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[Presentation] A Significant Role of Mesehchymal Stem Cells in Immune Processes and Pathogenic Fibrosis In Ocular Chronic Graft Versus Host Disease2011
Author(s)
Ogawa Y, Shimmura S, Morikawa S, Mabuchi Y, Yaguchi T, Inaba T, Kawakami Y, Okano H, Matsuzaki Y, Tsubota K
Organizer
The Association for Research in Vision and Ophthalmology (ARVO), Annual meeting
Place of Presentation
Florida, U.S.A.
Year and Date
2011-05-04
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[Presentation] Mucosal Microvilli In Dry Eye Patients With Chronic Graft-versus-host Disease2011
Author(s)
Tatematsu Y, Ogawa Y, Shinmura S, Dogru M, Nagai T, Yaguchi S, Yamazaki K, Kameyama K, Kawakami Y, Tsubota K
Organizer
The Association for Research in Vision and Ophthalmology (ARVO), Annual meeting
Place of Presentation
Florida, U.S.A.
Year and Date
2011-05-03
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