| Project/Area Number |
10670973
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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 |
Hematology
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| Research Institution | Kansai Medical University |
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Principal Investigator |
SUGIURA Kikuya Kansai Medical University, Medicine, Assistant Porfessor, 医学部, 講師 (30171143)
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| Co-Investigator(Kenkyū-buntansha) |
HISHA Hiroko Kansai Medical University, Medicine, Assistant Professor, 医学部, 講師 (90151422)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | hematopoietic stem cells / stromal cells / MHC rectriction / cobblestone colony / cell-to-cell interactio / 細胞間相互作用 / 増殖分化誘導 |
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| Research Abstract |
We have previously found that a significant number of hematopoietic progenitors accumulate in engrafted bones with the same MHC as the transplanted bone marrow cells. In the present study, to further clarify the MHC restriction between hematopoietic stem cells (HSC) and microenvironment, we carried out cobblestone colony formation assays by culturing HSCs-enriched bone marrow cells (5FU-resistant, Lin^-Sca1^+) with MHC-matched or-mismatched stromal cell monolayers. The formation of cobblestone colonies under MHC-mismatched stromal cells significantly decreased in comparison with MHC-matched stromal cells. However, the decrease in cobblestone colony formation under MHC-mismatched stromal cells was not significant when using MHC class Ideficient HSC or stromal cells. Taken together with the results using B10 congenic strains, it is suggested that the MHC preference is restricted by MHC class la molecules. Treatment with monoclonal antibodies (mAbs) against MHC class la molecules of stromal cell phenotypes significantly enhanced the cobblestone colony formation, whereas treatment with mAbs against HSC phenotypes significantly inhibited it. The expression of cytokines to promote hematopoiesis (such as stem cell factor, Flt3 ligand or basic fibroblast growth factor) was enhanced by the mAbs against stromal cell phenotypes. The enhancement of cytokine expression was also observed when stromal cells and HSCs were MHC-matched. These results suggest that signaling via the MHC molecules augments stromal cell activity and elicits the MHC restriction.
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