| Project/Area Number |
09357007
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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 |
Pediatrics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NAKAHATA Tatutoshi The University of Tokyo, The Insutitute of Medical Science, Professor, 医科学研究所, 教授 (20110744)
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| Co-Investigator(Kenkyū-buntansha) |
WATANABE Sumiko The University of Tokyo, The Insutitute of Medical Science, Research Associate, 助手 (60240735)
MAEKAWA Taira The University of Tokyo, The Insutitute of Medical Science, Lecturer, 医科学研究所, 講師 (80229286)
TSUJI Kohichiro The University of Tokyo, The Insutitute of Medical Science, Assocate Professor, 医科学研究所, 助教授 (50179991)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥27,500,000 (Direct Cost: ¥27,500,000)
Fiscal Year 1998: ¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1997: ¥20,500,000 (Direct Cost: ¥20,500,000)
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| Keywords | Self-renewal Factor / Mouse / Hematopoietic Stem Cell / Homan / AGM Region / Stromal Cell Line / CD34+ Cell / Cloning / サイトカイン / 臨床応用 / NOD / SCIDマウス / AGM-S3 / 遺伝子クローニング |
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| Research Abstract |
Recent studies on the developing mouse embryo have shown that long term-repopulating hematopoietic stem cells (LTR-HSC) are first identified in aorta-gonad-mesonephros (AGM) region at 10 days postcoitum (dpc), prior to such activity being observed in yolk sac and fetal liver, and expand in 11 dpc AGM region, suggesting that the AGM region at 10 to 11 dpc expresses the molecule(s) capable of supporting the expansion of HSC.In the present study, to detect such molecules, we established three stromal cell lines from 10.5 dpc AGM region, AGM-S1, S2 and S3 cells. The AGM-S3 cells possessed the capability to support the expansion of hematopoietic progenitors in culture with murine bone marrow cells without additional cytokines. The coculture of sorted mouse hematopoietic progenitors with AGM-S3 cells showed that these expanded progenitors were derived from lineage markars-negative (Lin^-) c-Kit^+Sca-1^+ primitive hematopoietic cells. AGM-S3 cells also supported for 6 weeks generation of huma
… More
n multipotential progenitors from CD34^+CD38^- primitive hematopoietic cells. Human LTR-HSC with the potential to reconstitute hematopoiesis in NOD/SCID mice were maintained on AGM-S3 cells for at least 4 weeks. Flowcytometric analysis showed that CD13, vascular cellular adhesion molecule-1 and Sca-1 were expressed on AGM-S3 cells. Although AGM-S3 cell expressed stem cell factor, Interleukin (IL)-6 and oncostatin M in reverse transcription polymerase chain reaction analysis, the combination of these cytokines could not stimulate the growth of human primitive hematopoietic cells. Therefore, AGM-S3 cells seem to express species-cross reactive molecule(s) other than the cytokines examined, which act on primitive hematopoietic progenitor/stem cells. This cell line is expected to elucidate molecular mechanisms regulating early hematopoiesis, and pave the way for developing strategies for expansion of human transplantable HSC.The cloning of the molecules expressing self-renewal factors on AGM-S3 cells are now under going. Less
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