Effect of G-CSF on hematopoietic stem cells derived from aplastic anemia patients in NOD/SCID/γc^<null> mice
| Project/Area Number |
15591103
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Nagoya University |
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Principal Investigator |
KOJIMA Seiji Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (20313992)
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| 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)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| 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)
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| Keywords | NOG mice / JMML / Aplastic Anemia / T cell / 7モノソミー / G-CSF |
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| 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.
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Report
(3 results)
Research Products
(28 results)
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[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)
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