R-spondin1の腸管保護による造血幹細胞移植の成績向上の試み

2008 Fiscal Year Annual Research Report

• Project/Area Number: 20659153
• Research Category: Grant-in-Aid for Exploratory Research
• Research Institution: Kyushu University
• Principal Investigator: 豊嶋 崇徳 Kyushu University, 大学病院, 准教授 (40284096)
• Keywords: GVHD / R-spondinl / 腸管

Research Abstract

MHC不適合のB6ドナーからB6D2F1レシピエントへの骨髄移植モデルにおいて移植day-3からday-1.day1からday3までR-spondin1200μgを静脈内投与した.腸管の移植前処置毒性を病理学的に検討したところ,R-spondin1投与群で腸管障害が軽度であった.またBrdU染色によって,R-spondin1投与群で腸管上皮細胞の増殖が認められた.移植後の血液中のlipopolysaccharide値はR-spondin1投与群で有意に低下しており,R-spondin1投与による腸管粘膜バリア機能の保持作用が示唆された.その結果,移植レシピエントの血清中TNF-αの低下がみられた.移植後の生存率を観察したところ,R-spondin1投与群で有意な生存率の改善がみられた.病理学的検索ではGVHDスコアの低下が確認された.以上の結果から,R-spondin1は移植前処置から腸管を保護し,その後のGVHDを軽減する可能性が示唆された.

Research Products

• [Journal Article] Infectious complications in chronic graft-versus-host disease : a retrospective study of 145 recipients of allogeneic hematopoietic stem cell transplantation with reduced- and conventional-intensity conditioning regimens (2008)
  • Author(s): Yamasaki S, Heike Y, Mori S, Fukuda T, Maruyama D, Kato R, Usui E, Koido K, Kim S, Tanosaki R, Tobinai K, Teshima T, Takaue Y
  • Journal Title: Transplant Infect Dis 10 Pages: 252-259
  • Peer Reviewed
• [Journal Article] Posttransplant administration of cyclophosphamide and donor lymphocyte infusion induces potent antitumor immunity to solid tumor (2008)
  • Author(s): Eto M, Kamiryo Y, Takeuchi A, Hirano M, Tatsugami K, Harada M, Kiyoshima K, Hamaguchi M, TeshimaT, Tsuneyoshi M, Yoshikai Y
  • Journal Title: Clin Cancer Res 14 Pages: 2833-40
  • Peer Reviewed
• [Journal Article] Reduced-intensity unrelated donor Bone Marrow Transplant for hematologic malignancies (2008)
  • Author(s): Kim S-W, Matsuo K, Fukuda T, Hara M, Matsue K, Taniguchi S, Eto T, Tanimoto M, Wake A, Hatanaka K, Nakao S, Ishid a Y, Harada M, Utsunomiya A, Imamura M, Kanda Y, Sunami K, Kawano F, Takaue Y, Teshima T
  • Journal Title: Int J Hematol 88 Pages: 324-330
  • Peer Reviewed
• [Journal Article] Preparation of functionally preserved CD4+CD25high regulatory T cells from leukapheresis products from ulcerative colitis patients, which are applicable to regulatory T cell-transfer therapy. (2008)
  • Author(s): Sumida Y, Nakamura K, Kanayama K, Akiho H, Teshima T, Takayanagi R
  • Journal Title: Cytotherapy 10 Pages: 698-710
  • Peer Reviewed
• [Presentation] T cell Toll-like receptors play a critical role in graft-versus-host disease and graft-versus-leukemia (2008)
  • Author(s): Kadowaki M, Aoyama K, Koyama M, Sakoda Y, Takeda K, Liu C, Akashi K, Tanimoto M, Teshima T
  • Organizer: 50^<th> Annual Meeting of The American Society of Hematology
  • Place of Presentation: 米国
  • Year and Date: 20081206-20081209
• [Presentation] Protection of the intestinal epithelium from conditioning with R-spondinl ameliorates graft-versus-host disease (2008)
  • Author(s): Takashima S, Aoyama K, Koyama M, Hashimoto D, Oshima T, Tomizuka K, Akashi K, Teshima T
  • Organizer: 50^<th> Annual Meeting of The American Society of Hematology
  • Place of Presentation: 米国
  • Year and Date: 20081206-20081209
• [Presentation] ドナーT細胞のToll-like receptor (TLR)シグナルはGVHDの重症化に関与する. (2008)
  • Author(s): 青山一利, 小山幹子, 橋本大吾, 佐古田幸美, 竹田潔, 赤司浩一, 原田実根, 谷本光音, 豊嶋崇徳
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 20081010-20081012