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2001 Fiscal Year Final Research Report Summary

Induction of organ transplantation tolerance using donor-derived peripheral blood stem cells and bone marrow transplantation

Research Project

Project/Area Number 11671179
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionNara Medical University

Principal Investigator

SAIHO Ko  Nara Medical University, Surgeryl, Research Assosiate, 医学部・第1外科, 助手 (80305713)

Co-Investigator(Kenkyū-buntansha) KANEHIRO Hiromich  Nara Medical University, Surgeryl, Research Assosiate, 医学部・第1外科, 助教授 (30204580)
Project Period (FY) 1999 – 2001
Keywordsperipheral blood stem cell / organ transplantation / tolerance / bone marrow transplantation / Small bowel transplantation / hepatocellular carcinoma / CD45 / chimerism
Research Abstract

We tried to induce donor-specific immune tolerance using donor-derived hematopoietic cells and bone marrow chimerism, which may lead to clonal deletion. G-CSF mobilized peripheral blood hematopoietic stem cells have reduced costimulatory function, which may induce anergy of allergenic T cells. Allergenic donor-derived hematopoietic stem cells could not be accepted ithout preconditioning of the recipient, even after modification with hematopoietic cytokines. Then preconditioning regimens using cyclophosphamide (CYP) monotherapy were evaluated. High dose CYP induced stable hematopoietic chimerism, but the recipient developed severe GVHD. Modification of donor-derived hematopoietic stem cells with various kinds of cytokines resulted in long-lasting bone marrow chimerism by non-lethal dose of CYP preconditioning. GVHD was avoided with this modification. Chimeric recipients accepted heart allograft from bone marrow donor strain without immunosuppression. Preconditioning with anti-CD45 monoclonal antibody (mAb) also induced hematopoietic chimerism. The anti-CD45 mAb enhanced donor-derived passenger leukocytes and induced heart allograft acceptance. We also focused on characteristic feature of small bowel allograft which have abundant donor-derived lymphocytes in the mesenteric lymph nodes (MLNs). Significance of immune interaction between donor and recipient lymphocytes in the garft MLNs was shown. Modification of costimulatory function of donor-derived spleen cells resulted in donor-specific immunosuppression. The immunosuppressive effect of composite liver allograft, which contained a lot of donor-derived passenger leukocytes, was also shown in a rat liver/small bowel allograft model. Tolerance induction is beneficial especially for patients with malignant tumor, because immunosuppression may promote tumor progression. Then we studied indication of liver transplantation for patients with hepatocellular carcinoma.

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Saiho Ko, et al.: "Manipulation of CD45 in transplomtation telerana"Current Molecular Medicine. 2(in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Saiho Ko, et al.: "Liver fibrosis murease the risk of intra hepatic reurence ofter hepatectony for hepatocellular corcinomr"Biotish Journal of Surgery. 89. 57-62 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Saiho Ko, et al.: "Long-ferm allos rats acopeance in dnced by single dase anci-leukocyte common ancigen(RT7) antibody in therat"Transplantation. 71. 1124-1131 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Saiho Ko, et al.: "Bois marrrow aplasia induced by passergen leukocytes from beart allog rafts"Experimental hematology. 29. 339-344 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yukihiro Tatekawa, et al.: "Intergraft expression of p38 and activated p38 MAPK (mitosen-achivated protein kinase) in rat small bowel transplantation"Transplantation International. 32. 1281-1282 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tung-Yu Tsui, et al.: "Specific immunosuppression by postoperative infusion of allogeneic spleen cells"Transplantation. 69. 25-35 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ko S, Jager MD, Dahlke MH, Nakajima Y, Schlitt HJ.: "Mnipulation of CD45 in transplantation tolerance"Curr Mol Med. 2(in press). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ko S, Kanehiro H, Hisanaga M. Nagao M, Ikeda N, Nakajima Y: "Liver fibrosis increases the risk of intrahepatic recurrence after hepatectomy for hepatocellular carcinoma"Br J Surg. 89. 57-62 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ko S, Jager MD, Tsui TY, Deiwick A, Dinkel A, Rhode F, Dahlke MH, et al.: "Lomg-term allograft acceptance induced by single dose anti-leukocyte common antigen (RT7) antibody in the rat"Transplantation. 71. 1124-1131 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ko S, Dahlke MH, Lauth 0, Jager MD, Deiwick A, Dinkel A, Tsui TY, et al.: "Bone marrow aplasia Induced by passenger leukocytes from heart allografts"Exp Hematol. 29. 339-344 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatekawa Y, Kanehiro H, Dohi Y, Yamada T, Kanokogi H, Nakajima Y, Ko S, Hisanaga M, Aomatsu Y, Nakano H: "Intragraft expression of p38 and activated p38 MAPK (mitogen-activated protein kinase) in rat small bowel transplantation"Transplant Int. 14. 211-216 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tatekawa Y, Kanehiro H, Kanokogi H, Nakajima Y, Ko S, Hisanaga M, Aomatsu Y, et al.: "Intragraft expression of p38 in rat small bowel transplantation"Transplant Proc. 32. 1281-1282 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tsui TY, Deiwick A, Ko S, Schlitt HJ.: "Specific immunosuppression by postoperative infusion of allogeneic spleen cells"Transplantation. 69. 25-35 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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