| Project/Area Number |
07557077
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Hematology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
NAKAUCHI Hiromitsu University of Tsukuba, Institute of Basic Medical Science, Professor, 基礎医学系, 教授 (40175485)
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| Co-Investigator(Kenkyū-buntansha) |
IMAI Hiroshi 農林水産省畜産試験場, 細胞操作研究室, 室長
NAKAMURA Yukio University of Tsukuba, Institute of Basic Medical Science, Lecture, 基礎医学系, 講師 (60231479)
TOKUMOTO Yasuhito University of Tsukuba, Institute of Basic Medical Science, Research Associate (70261170)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥16,000,000 (Direct Cost: ¥16,000,000)
Fiscal Year 1997: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1996: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1995: ¥9,000,000 (Direct Cost: ¥9,000,000)
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| Keywords | Hematopoietic stem cells / GM-CSF / IL-3 / swine / transgenic mice / SCID mice / Myelodysplastic syndrome / NK cells. / 自己複製 / サイトカイン / G-CSF / GM- CSF |
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| Research Abstract |
1.Engraftment of human hematopoietic cells in transgenic Severe Combined Immunodeficient mice.
A transgenic SCID (TG-SCID) mouse expressing the human cytokines interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) has been generated with the aim of making a model system allowing the in vivo proliferation of human hematopoietic cells. Using TG-SCID mice expressing high levels (30-35 ng/ml in the serum) of human GM-CSF and IL-3, we attempted to engraft a human myeloid leukemia cell line, F-36P,derived from a myelodysplastic syndrome (MDS) patient. When F-36P cells were transferred intravenously into sublethally irradiated TG-SCID mice, extensive proliferation of F-36P cells was found four to six weeks later. Successful engraftment, however, required the pre-administration of a monoclonal antibody to mouse interleukin-2 receptor (IL-2R) beta chain, neutralizing NK activity. Surprisingly, all of the transplanted TG-SCID mice engrafted with F-36P cells developed
… More
hind leg paralysis approximately 6 weeks after transfer. Histological analysis demonstrated extensive invasion and formation of osteolytic lesions by the F-36P cells in the vertebrae. These data indicate that transgenic SCID mice expressing human IL-3 and GM-CSF provide a useful system for the study of human leukemia. In addition, NK cells appear to play an important role in rejection of human cells.
2.Transplantation of human hematopoietic cells into miniature-swine and swine fetus
To establish a model for a long-term human hematopoietic reconstitution, human bone marrow or cord blood cells were transplanted into day 45-81 miniature swine or swine fetuses through uterine wall of a pregnant mother. Of the 15 pregnant animals to which transplantation of human hematopoietic cells was performed, five of them gave birth. New born pigs were examined periodically for the presence of human CD45_+ blood cells in peripheral blood and in bone marrow. So far, none of them have human CD45_+ cells above 1% level either in PB or in bone marrow. Less
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