| Project/Area Number |
11670763
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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 | HIROSHIMA UNIVERSITY |
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Principal Investigator |
KOBAYASHI Masao FACULTY OF EDUCATION, CHILD HEALTH, HIROSHIMA UNIVERSITY, PROFESSOR, 教育学部, 教授 (00162016)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Takashi FACULTY OF MEDICINE, HIROSHIMA UNIVERSITY, ASSISTANT, 医学部, 助手 (90271064)
KATOH Osamu RESEARCH INSTITUTE FOR RADIATION BIOLOGY AND MEDICINE, HIROSHIMA UNIVERSITY, ASSOCIATE PROFESSOR, 原爆放射能医学研究所, 助教授 (90214361)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Hematopoietic progenitors / Hematopoietic factors / Coculture / Xenogeneic transplantation / Stromal cell / Congenital Neutropenia |
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| Research Abstract |
We have tested the effects of coculture of purified bone marrow cells with stromal cells on the capability of repopulating in NOD/SCID mice. Primitive human bone marrow cells were purified based on the expression of CD34, Kit receptor and CD38 using the FACS Vantage. Bone marrow stromal cells were established by the adherence on dishes. The engraftment of human purified bone marrow cells were observed when mice were pretreated with the injection of stromal cells and CTLA4-Ig inducing anergy against human blood cells. The primitive bone marrow cells cultured on the stromal cells enhanced the number of colony-forming cells and the sruvival. The addition of stem cell factor, the ligand for flk2/flt3 and thrombopoietin to the coculture system significantly incrreased the number of colony-forming cells. Then, we tested NOD/SCID mice-repopulating ability of cells expanded by the hematopoietic factors and stromal cells. However, none of mice transplanted with expanded cells showed successful engraftment. These observations suggest the requirement of appropriate culture conditions for expanding the primitive bone marrow cells capable repopulating in NOD/SCID mice.
Furthermore, we studied the expression of granulocyte colony-stimulating factor receptor (G-CSFR) in primitive myeloid progenitor cells and their responsiveness to hematopoietic factors to define the basis for the faulty granulopoiesis in patients with severe congenital neutropenia (SCN), . The results demonstrate that the presence of qualitative and quantitative abnormalities of primitive mveloid progenitor cells expressing G-CSFR may play an important role in the impairment of granulopoiesis in patients with SCN.
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