Development of a novel therapy for chronic GVHD targeting a macrophage-myofibroblast axis in fibrotic process
Project/Area Number |
17K09945
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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 |
Hematology
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Research Institution | Hokkaido University |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | 慢性移植片対宿主病 / 線維化 / マクロファージ / ドライアイ / 筋線維芽細胞 / HSP47 / GVHD / 同種造血幹細胞移植 / ドライアイ症候群 / 線維芽細胞 / リポソーム / 慢性GVHD / 移植片対宿主病 |
Outline of Final Research Achievements |
In the current study, we developed a novel anti-fibrotic therapy for chronic GVHD using murine model of allogeneic bone marrow transplantation. We found that macrophage depletion using anti-CSF1R antibody ameliorated skin fibrosis in chronic GVHD. We also found that systemic administration of vitamin A coupled liposomes containing siRNA against HSP47 (VA-lip HSP47) could ameliorate fibrosis in the skin, lacrimal gland, and salivary gland in chronic GVHD. Finally, we found that ocular instillation of VA-lip HSP47 ameliorate lacrimal grand fibrosis and dry eye syndrome in chronic GVHD.
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Academic Significance and Societal Importance of the Research Achievements |
同種造血幹細胞移植の技術の進歩により, より多く移植が行われるようになり, より多くの移植患者の長期生存が可能となっている。そのため慢性GVHDによる生活の質の低下を防ぐことはより重要になっている。本研究では, 免疫抑制剤を使用せず線維化のメカニズムを標的にした新しい慢性GVHD治療法を開発した。これにより, 感染症や腫瘍の再発を増加させずに, 慢性GVHDの治療を行える可能性がある。
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Short-term KRP203 and posttransplant cyclophosphamide for graft-versus-host disease prophylaxis.2020
Author(s)
Yokoyama E, Hashimoto D, Hayase E, Ara T, Ogasawara R, Takahashi S, Ohigashi H, Tateno T, Hasegawa Y, Chen X, Teshima T.
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Journal Title
Bone Marrow Transplant.
Volume: 55
Issue: 4
Pages: 787-795
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Histological and magnified endoscopic evaluation of villous atrophy in gastrointestinal graft-versus-host disease.2020
Author(s)
Matsuda K, Ono S, Tanaka I, Inoue M, Kinowaki S, Ishikawa M, Tsuda M, Yamamoto K, Shimizu Y, Takahashi S, Hayase E, Hashimoto D, Teshima T, Sakamoto N.
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Journal Title
Ann Hematol.
Volume: ー
Issue: 5
Pages: 1121-1128
DOI
Related Report
Peer Reviewed
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[Journal Article] Ocular instillation of vitamin A-coupled liposomes containing HSP47 siRNA ameliorates dry eye syndrome in chronic GVHD.2019
Author(s)
Ohigashi, H., Hashimoto, D., Hayase, E., Takahashi, S., Ara, T., Yamakawa, T., Sugita, J., Onozawa, M., Nakagawa, M., Teshima, T.
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Journal Title
Blood Adv.
Volume: 3
Issue: 7
Pages: 1003-1010
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Intestinal Lymphatic Endothelial Cells Produce R-Spondin32018
Author(s)
Ogasawara Reiki、Hashimoto Daigo、Kimura Shunsuke、Hayase Eiko、Ara Takahide、Takahashi Shuichiro、Ohigashi Hiroyuki、Yoshioka Kosuke、Tateno Takahiro、Yokoyama Emi、Ebata Ko、Kondo Takeshi、Sugita Junichi、Onozawa Masahiro、Iwanaga Toshihiko、Teshima Takanori
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Journal Title
Scientific Reports
Volume: 8
Issue: 1
Pages: 1-9
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease2017
Author(s)
Hayase E, Hashimoto D, Nakamura K, Noizat C, Ogasawara R, Takahashi S, Ohigashi H, Yokoi Y, Sugimoto R, Matsuoka S, Ara T, Yokoyama E, Yamakawa T, Ebata K, Kondo T, Hiramine R, Aizawa T, Ogura Y, Hayashi T, Mori H, Kurokawa K, Tomizuka K, Ayabe T, Teshima T
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Journal Title
J Exp Med
Volume: 214
Issue: 12
Pages: 3507-3518
DOI
NAID
Related Report
Peer Reviewed
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