“造血幹細胞異常症"の病因の解析と骨髄移殖による治療の為の基礎的研究

• Project/Area Number: 63480147
• Research Category: Grant-in-Aid for General Scientific Research (B)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Kansai Medical University
• Principal Investigator: IKEHARA Susumu Kansai Med. Univ. Department of Pathol. Professor, 医学部, 教授 (90108986)
• Co-Investigator(Kenkyū-buntansha): OGATA Hajime Kansai Med. Univ. Department of Pathol. Instructor, 医学部, 助手 (50169174) ; HISHA Hiroko Kansai Med. Univ. Department of Pathol. Instructor, 医学部, 助手 (90151422) ; TOKI Junko Kansai Med. Univ. Department of Pathol. Instructor, 医学部, 助手 (40077681) ; NAGATA Norikazu Kansai Med. Univ. Department of Pathol. Lecturer, 医学部, 講師 (40155940) ; INABA Muneo Kansai Med. Univ. Department of Pathol. Lecturer, 医学部, 講師 (70115947) ; 安水 良知 関西医科大学, 医学部, 講師 (00142753)
• Project Period (FY): 1988 – 1990
• Project Status: Completed (Fiscal Year 1991)
• Budget Amount: ¥6,600,000 (Direct Cost: ¥6,600,000); Fiscal Year 1990: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 1989: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 1988: ¥4,200,000 (Direct Cost: ¥4,200,000)
• Keywords: Bone Marrow Transplantation / Autoimmune Diseases / Animal Models / 免疫学的寛容 / マウス / Stromal cell / 骨移植 / Natural Suppressar Cell / 胸腺リンパ腫 / 血小板減少性紫斑病 / 白血病

Research Abstract

1)We have succeeded in transferring not only systemic autoimmune diseases but also organ-specific autoimmune diseases to normal mice by transplantation of hemopoietic stem cells purified from autoimmune-prone mice.
i)Transplantation of hemopoietic stem cells from NOD mice to C3H/HeN mice induces insulin-dependent diabetes mellitus in C3H/HeN mice.
ii)Transplantation of hemopoietic stem cells from(NZW x BXSB)F_1 mice to C3H/HeN or C57BL/6j mice induces imme thrombocytopenic purpura and lupus nbphritis in C3H/HeN or C57BL/6j mice.
2)We have found that hemopoietic stem cells in the cycling phase inhibit the proliferation of tumor cells, and that such cells are present in the bone marrow of monkeys and humans.
3)We have established autoreactive clones from MRL/lpr mice.
4)We have found that Ly-1 B cells in the thymus play a crucial role in the tolerance induction in the Mls system.

Research Products

• [Publications] S.Ikehara et al.: "Organ-specific and systemic systemic autoimmune diseases originate from defects in hemopoietic stem cells." Proc.Natl.Acad.Sci.87. 8341-8344 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] H.Mizutani et al.: "Analyses of thrombocytopenia in ideopathic thrombocytopenic purpuraprone mice by platelet transfer experiments between(NWZ x BXSB)and normal mice." Blood. 75. 1809-1812 (1990)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] S.Ikehara et al.: "Long-term observations of autoimmune-prone mice treated for autoimmune disease by allogenic bone marrow transplanttion." Proc.Natl.Acad.Sci.86. 3306-3310 (1989)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] N.Oyaizu et al.: "(NZW x BXSB)F1 mouse.A new animal model of ideopathic thrombocytopeeic purpura." J.Exp.Med.167. 2017-2022 (1988)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] K.Sugiura et al.: "Wheat germ agglutinin-positive cells in a stem cell-enriched fraction of mouse bone marrow have potent natural supperssor activity." Proc.Natl.Acad.Sci.85. 4824-4826 (1988)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] M.iNaba et al.: "Isolation of murine pluripotent hemopoietic stem cells in the G0 phase." Biochem.Biophys.Res.Commun.147. 687-694 (1987)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] S. Ikehara et al: "Organ-specific and systemic autoimmune diseases originate from defects in hemopoietic stem cells." Proc. Natl. Acad. Sci.87. 8341-8344 (1990)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] H. Mizutani et al: "Analyses of thrombocytopenia in idiopathic thrombopathic purpura-prone mice by platelet transfer experiments between (NZWxBXSB) and normal mice." Blood. 75. 1809-1812 (1990)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] S. Ikehara et al: "Long-term observations of autoimmune-prone mice treated for autoimmune diseases by allogenic bone marrow transplantation." Proc. Natl. Acad. Sci.86. 3306-3310 (1989)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] N. Oyaizu et al: "(NZWxBXSB) F1 mouse. A new animal model of idiopathic thrombocytopenic purpura." J. Exp. Med.167. 2017-2022 (1988)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] K. Sugiura et al: "Wheat germ agglutinin-positive cells in a stem cell-enriched fraction of mouth bone marrow have potent natural suppresser activity." Proc. Natl. Acad. Sci.85. 4824-4826 (1988)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] M. Inaba et al: "Isolation of murine pluripotent hemopoietic stem cells in the G0 phase." Biochem. Biophys. Res. Commun.147. 687-694 (1987)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] S.Ikehara et al.: "Organーspecific and systemic autoimmune diseases originate from defects in hemopoietic stem cells." Proc.Natl.Acad.Sci.87. 8341-8344 (1990)
• [Publications] H.Mizutani et al.: "Analyses of thrombocytopenia in idiopathic thrombocytopenic purpuraprone mice by platelet transfer experiments between(NZWxBXSB)and normal mice." Blood. 75. 1809-1812 (1990)
• [Publications] S.Ikehara et al.: "Longーterm observations of autoimmunneーprone mice treated for autoimmune disease by allogenic bone marrow transplantation." Proc.Natl.Acad.Sci.86. 3306-3310 (1989)
• [Publications] N.Oyaizu et al.: "(NZW x BXSB)F1 mouse.A new animal model of idiopathic thrombocytopenic purpura." J.Exp.Med.167. 2017-2022 (1988)
• [Publications] K.Sugiura et al.: "Wheat germ agglutininーpositive cells in a stem cellーenriched fraction of mouth bone marrow have potent natural suppressor activity." Proc.Natl.Acad.Sci.85. 4824-4826 (1988)
• [Publications] M.Inaba et al.: "Isolation of murine pluripotent hemopoietic stem cells in the GO phase." Biochem.Biophys.Res.Commun.147. 687-694 (1987)
• [Publications] Miyama-Inba Muneo et al.: "Unusual pheotype of B cells in the thymus of normal mice." J.Exp.Med.168. 811-816 (1989)
• [Publications] Ikehara Susumu et al.: "Long-term observations of autoimmune-prone mice treated for autoimmune diseases by allogeneic bone marrow transplantation." Proc.Natl.Acad.Sci.86. 3306-3310 (1989)
• [Publications] Inaba Muneol et al.: "Functional analyses of thymic CD^<5+> cells.Responsiveness to MHC class II-restricted T blasts but not to lpr or anti-IgM plus IL-4." J.Exp.Med.171. 321-326 (1990)
• [Publications] Sugiura Kikuya et al.: "Inhibition of tumor cell proliferation by natural suppressor cells present in murine bone marrow." Cancer Research.
• [Publications] Sugiura Kikuya et al.: "Enrichment of natural suppressor activity in a wheat germ agglutinin positive, stem cell enriched fraction of monkey bone marrow." Blood.
• [Publications] Mizutani Hajime et al.: "Analyses of thrombocytopenia in idiopahtic thrombocytopenic purpuraprone mice by platelet transfer experiments between(NZW×BXSB)F_1and normal mice." Blood.
• [Publications] 池原進(山村雄一編集): "最新免疫学" 同文書院, 806 (1990)
• [Publications] Susumu IKEHARA,: Immunopathology Immunotherapy Forum. 10. 2-7 (1988)
• [Publications] Ryoji YASUMIZU,et al.: The Journal of Immunology. 141. 2181-2186 (1988)
• [Publications] Muneo INABA,et al.: The Journal of Experimental Medicine. 168. 811-816 (1988)
• [Publications] Naoki OYAIZU,et al.: The Journal of Experimental Medicine. 167. 2017-2022 (1988)
• [Publications] Kikuya SUGIURA,et al.: Proc.Natl.Acad.Sci.,U.S.A.85. 4824-4826 (1988)
• [Publications] Susumu IKEHARA,et al.: Proc.Natl.Acad.Sci.,U.S.A.
• [Publications] 池原進: "免疫の研究8.免疫病発症機序の遺伝的背景" 同文書院,