A significant role of senescent cells and donor mesenchymal stem cells in ocular chronic graft-versus-host disease and development of new therapy
Project/Area Number |
26462668
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Ophthalmology
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Research Institution | Keio University |
Principal Investigator |
Ogawa Yoko 慶應義塾大学, 医学部(信濃町), 特任准教授 (30160774)
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Co-Investigator(Renkei-kenkyūsha) |
Kazuo Tsubota 慶應義塾大学, 医学部, 教授 (40163878)
Shimmura Shimmura 慶應義塾大学, 医学部, 准教授 (00235780)
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | 眼GVHD / ドライアイ / 間葉系幹細胞 / 細胞老化 / 慢性移植片対宿主病 / 角膜 / 涙腺 / 造血幹細胞 / 免疫 / 線維化 / 眼免疫 / 老化細胞 / 造血幹細胞移植 / マクロファージ / 免疫応答 |
Outline of Final Research Achievements |
We found that a significant role of mesenchymal stem cells(MSCs)and senescent macrophages in the pathogenic fibrosis in ocular graft-versus-host disease (GVHD). Donor MSCs and senescent macrophages expressing p16 were infiltrated into lacrimal glands and activated by interacting each other in early onset of ocular GVHD by secreting senescent related factors. We confirmed immunogenic and MHC class II+ MSCs infiltrated into cGVHD target organs especially lacrimal gland. We analysed the effectiveness of depletion of MSCs transplantation or suppression of a senescent associated cytokine in development of fibrosis and inflammation in ocular GVHD.
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Report
(4 results)
Research Products
(47 results)
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[Journal Article] Comparison of performance of the 2016 ACR-EULAR classification criteria for primary Sjogren’s syndrome with other sets of criteria in Japanese patients.2017
Author(s)
Tsuboi H., Hagiwara S., Asashima H., Takahashi H., Harota T., Noma H., Umehara H., Kawakami A., Nakamura H., Sano H., Tsubota K., Ozawa 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
Ann. Rheum. Dis.
Volume: 3
Issue: 12
Pages: 2016-210758
DOI
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] MHC-compatible bone marrow stromal/stem cells trigger fibrosis by activating host T cells in a scleroderma mouse model.2016
Author(s)
Ogawa Y, Morikawa S, Okano H, Mabuchi Y, Suzuki S, Yaguchi T, Sato Y, Mukai S, Yaguchi S, Inaba T, Okamoto S, Kawakami Y, Tsubota K, Matsuzaki Y, Shimmura S.
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Journal Title
DOI
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Comparisons for grading chronic ocular graft-versus-host disease: NIH eye score, Japanese dry eye score, and DEWS 2007 score.2014
Author(s)
Tatematsu Y, Ogawa Y, Abe T, Kamoi M, Uchino M, Saijyo-Ban Y, Yaguchi S, Mukai S, Mori T, Okamoto S, Tsubota K.
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Journal Title
Sci Rep.
Volume: 4
Issue: 1
Pages: 6680-6680
DOI
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye.2014
Author(s)
Inaba T, Hisatsune C, Sasaki Y, Ogawa Y, Ebisui E, Ogawa N, Matsui M, Takeuchi T, Mikoshiba K, Tsubota K.
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Journal Title
PLoS One.
Volume: 9
Issue: 6
Pages: e99205-e99205
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Primary and secondary surveys on epidemiology of Sjogren's syndrome in Japan2014
Author(s)
Tsuboi, H. Asashima, H. Takai, C. Hagiwara, S. Hagiya, C. Yokosawa, M. Hirota, T. 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. Yoshifuji, H. Ohta, A. Matsumoto, I. Sumida, T.
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Journal Title
Mod Rheumatol
Volume: 24
Issue: 3
Pages: 464-70
DOI
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Peer Reviewed / Open Access
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[Presentation] 眼慢性移植片対宿主病の国際診断基準の感度と特異度の検討.2015
Author(s)
福井正樹, 小川葉子, レザ ダナ, キム ステラ, ビクター ペレッツ, 立松由佳子, 山根みお, 小川護, 西條裕美子, 鴨居瑞加, 坪田一男.
Organizer
第69回日本臨床眼科学会
Place of Presentation
名古屋国際会議場(愛知県名古屋市熱田区)
Year and Date
2015-10-22
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[Presentation] Comparison of 3 Measurement Scales for Grading Ocular Chronic Graft-Versus-Host Disease Patients2014
Author(s)
Tatematsu Y, Ogawa Y, Abe T, Kamoi M, Uchino M, Saijyo-Ban Y, Yaguchi S, Mori T, Okamoto S, Tsubota K.
Organizer
World Ophthalmology Congress of the International Council of Ophthalmology (WOC2014)
Place of Presentation
Tokyo, Japan
Year and Date
2014-04-02 – 2014-04-06
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[Book] 眼科2016
Author(s)
中山直彦, 小川葉子, 大高 功, 坪田一男.
Publisher
金原出版株式会社
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