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Effect of G-CSF on hematopoietic stem cells derived from aplastic anemia patients in NOD/SCID/γc^<null> mice

Research Project

Project/Area Number 15591103
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionNagoya University

Principal Investigator

KOJIMA Seiji  Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (20313992)

Co-Investigator(Kenkyū-buntansha) NAOE Tomoki  Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (50217634)
KAMACHI Yoshiro  Nagoya University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (20343204)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsNOG mice / JMML / Aplastic Anemia / T cell / 7モノソミー / G-CSF
Research Abstract

NOD/SCID/γc^<null>(NOG) mice is a recently developed immunodeficient mouse which lack not only T cell and B cell activity but also NK cell activity. Multilinege differentiation of normal human stem cells is well supported in this mouse model. We tried to transplant to bone marrow cells from patients with juvenile myelomonocytic leukemia(JMML) and aplastic anemia(AA) into NOG mice and produce xenograt model mice.
Using this model mice, we demonstrated the engraftment of multilinege human cells in the murine bone marrow and spleen. The FISH method showed the clonal marker in purified CD3^+,CD19^+,and CD56^+ subpopulations. Those findings support the concept that JMML orginates in multilinege hematopoietic stem cells. We also demonstrated the engraftment of human cells in NOG mice transplanted with mononuclear cells derived from patients AA. Different from mice transplanted with stem cells from patients with JMML, most of the engrafted cells belonged to T cell lineage. Mice developed pancytopenia and bone marrow findings are compatible with those of AA. Human cells did not engraft when T cell depleted mononuclear cells were transfused. T cell is indispensable to cause bone marrow failure in this model mice.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (28 results)

All 2005 2004 2003 Other

All Journal Article (15 results) Publications (13 results)

  • [Journal Article] Difference between T Cell-Type and Natural Killer Cell-Type Chronic Active Epstein-Barr Virus Infection.2005

    • Author(s)
      Kimura H, Kojima S, et al.
    • Journal Title

      J Infect Dis. 191

      Pages: 531-539

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Presence of anti-kinection and anti-PMS1 antibodies in Japanese aplastig anemia patients.2005

    • Author(s)
      Hirano N, Kojima S, et al.
    • Journal Title

      Br J Haematol. 128

      Pages: 221-223

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Difference between T Cell-Type and Natural Killer Cell-Type Chronic Active Epstein-Barr Virus Infection.2005

    • Author(s)
      Kimura H, Kojima S, et al.
    • Journal Title

      J Infect Dis 191

      Pages: 531-539

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Presence of anti-kinection and anti-PMS1 antibodies in Japanese aplastic anemia patients.2005

    • Author(s)
      Hirano N, Kojima S, et al.
    • Journal Title

      Br J Haematol 128

      Pages: 221-223

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Presence of anti-kinection and anti-PMS1 antibodies in Japanese aplastic anemia patients.2005

    • Author(s)
      Hirano N, Kojima S, et al.
    • Journal Title

      Br J Haematol. 128

      Pages: 221-223

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expansion of human CMV-specific cytotoxic T lymphocytes to a clinical scale : a simple culture system using tetrameric HLA-peptide complexes.2004

    • Author(s)
      Watanabe N, Kojima S, et al.
    • Journal Title

      Cytotherapy. 6

      Pages: 514-522

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Diamond-Blackfan Anemia in Japan : Clinical Outcome of Prednisolone Therapy and Hematopoietic Stem Cell Transplantation.2004

    • Author(s)
      Ohga S, Kojima S, et al.
    • Journal Title

      Int J Hematol. 79

      Pages: 22-30

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Expansion of human CMV-specific cytotoxic T lymphocytes to a clinical scale : a simple culture system using tetrameric HLA-peptide complexes.2004

    • Author(s)
      Watanabe N, Kojima S, et al.
    • Journal Title

      Cytotherapy 6

      Pages: 514-522

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Diamond-Blackfan Anemia in Japan : Clinical Outcome of Prednisolone Therapyand Hematopoietic Stem Cell Transplantation.2004

    • Author(s)
      Hirano N, Kojima S, et al.
    • Journal Title

      Int J Hematol 79

      Pages: 22-30

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Twenty years' experience in allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in the Nagoya Blood and Marrow Transplantation Group.2004

    • Author(s)
      Iida H, Kojima S, et al.
    • Journal Title

      Int J Hematol. 79

      Pages: 79-84

    • NAID

      50000391299

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Quantitative Analysis of Epstein-Barr Virus(EBV)-Specific CD8+T Cell in patients with Chronic Active EBV Infection.2004

    • Author(s)
      Sugaya N, Kojima S, et al.
    • Journal Title

      J Infect Dis. 190

      Pages: 985-989

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Autoantibodies frequently detected in patients with aplastic anemia.2003

    • Author(s)
      Hirano N, Kojima S, et al.
    • Journal Title

      Blood 102

      Pages: 4567-4575

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Induction of Complete Remission of Hypoplastic Leukemia with Antithymocyte Globulin.2003

    • Author(s)
      Yoshimi A, Kojima S, et al.
    • Journal Title

      Int J Hematol. 77

      Pages: 277-281

    • NAID

      50000824734

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Autoantibodies frequently detected in patients with aplastic anemia.2003

    • Author(s)
      Hirano N, Kojima s, et al.
    • Journal Title

      Blood 102

      Pages: 4567-4575

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Induction of Complete Remission of Hypoplastic Leukemia with Antithymocyte Globulin.2003

    • Author(s)
      Yoshimi A, Kojima S, et al.
    • Journal Title

      Int J Hematol 77

      Pages: 277-281

    • NAID

      50000824734

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] 小島 勢二: "実践 小児診療 「血液疾患,悪性腫瘍」"日本医師会雑誌. 129. 248-264 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 小島 勢二: "再生不良性貧血"小児内科. 35. 1147-1152 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 小島 勢二: "造血幹細胞移植"医学のあゆみ. 206. 655-659 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iida H, Sao H, Kitaori K, Gotoh S, Yazaki M, Kojima S, Wakita A, Morishima Y, Kodera Y, Morishita Y: "Twenty years' experience in allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia in the Nagoya Blood and Marrow Transplantation Group"Int J Hematol. 79. 79-84 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohga S, Mugishim H, Ohara A, Kojima S, Fujisawa K, Yagi K, Higashigawa M, Tsukimoto I, Aplastic Anemia Committee Japanese Society of Pediatric Hematology: "Diamond-Blackfan anemia in Japan : clinical outcomes of prednisolone therapy and hematopoietic stem cell transplantation"Int J Hematol. 79. 22-30 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Maeda N, Kato K, Matsuyama T, Kojima S, Ohyama K: "High-Dose Busulfan is a Major Risk Factor for Ovarian Dysfunction in Girls After Stem Cell Transplantation"Clin Pediatr Endocrinol. 12. 13-18 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirose Y, Kudo K, Kiyoi H, Hayashi Y, Naoe T, Kojima S: "Comprehensive analysis of gene alterations in acute megakaryo blastic leukemia of Down's syndrome"Leukemia. 17. 2250-2252 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hirano N, Butler MO, von Bergwelt-Baildon MS, Maecker B, Schultze JL, O'Connor KC, Schur PH, Kojim S, Guinan EC, Nadler LM: "Autoantibodies frequently detected in patients with aplastic anemia"Blood. 102. 4567-4575 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Xu G, Nagano M, Kanezaki R, Toki T, Hayashi Y, Taketani T, Taki T, Mitui T, Koike K, Kato K, Imaizumi M, Sekine I, Ikeda Y, Hanada R, Sako M, Kudo K, Kojima S, Ohneda O, Yamamoto M, Ito E: "Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down syndrome"Blood. 102. 2960-2968 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshimi A, Nakamoto C, Nakamura Y, Kato K, Matsuyama T, Kudo K, Kojima S: "Induction of complete remission of hypoplastic leukemia with antithymocyte globulin"Int J Hematol. 77. 277-281 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 小島勢二: "今日の治療指針 小児の鉄欠乏性貧血"医学書院. 1669 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 工藤寿子, 小島勢二: "小児白血病診療ハンドブツク Down症候群に発症した白血病"中外医学社. 396 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 小島勢二: "小児血液・腫瘍疾患治療プロトコール集 再生不良性貧血"医薬ジャーナル社. 355 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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