Project/Area Number |
13470157
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pediatrics
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Research Institution | The University of Tokyo |
Principal Investigator |
TSUJI Kouichiro The University of Tokyo, The Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (50179991)
|
Co-Investigator(Kenkyū-buntansha) |
EBIHARA Yasuhiro The University of Tokyo, The Institute of Medical Science, Assistant, 医科学研究所, 助手 (40302608)
|
Project Period (FY) |
2001 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2002: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 2001: ¥8,500,000 (Direct Cost: ¥8,500,000)
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Keywords | Regenerative medicine / Organogenesis / Generation of hematopoiesis / Yolk sac / AGM region / CD34 / Hematopoietic stem cell / Fetal therapy / 造血 / 全胚胎児培養 / 血管内皮細胞 / 二次造血 / 全胚培養 / B細胞 / OP9ストローマ細胞 / キメラ胎仔マウス |
Research Abstract |
In this project, we indicated the following results according mouse embryonic hematopoiesis. (1)In mouse embryogenesis, the primitive hematopoiesis in 7.5 days postcoitum (dpc) yolk sac (YS) has megakryocytopoiesis different from that of the definitive hematopoiesis in adult bone marrow. (2)Stromal cells derived from aorta-gonad-mesonephros (AGM) region in 10.5 dpc mouse embryo can support the development of hematopoietic stem cells (HSC) in the definitive hematopoiesis. (3)The Stromal cells from AGM region in 10.5 dpc mouse embryo can stimulate the generation of definitive hematopoiesis from not only AGM region but also YS at 8.0 dpc, a time when YS and embryo are not connected by blood vessels. (4)8.25 dpc mouse YS was engrafted upon YS of donor embryo at the same stage to make YS-YS chimeric embryo. After the incubation of the chimeric embryo for 66 hours, we identified B cells originated from donor YS in the chimera, suggesting that a part of definitive hematopoiesis at least is generated from YS in mouse embryogenesis. (5) The stromal cells are also capable of supporting the development of cord blood HSC derived from human fetal hematopopiesis. (6) While CD34 is expressed on c-Kit+ HSC in mouse fetuses and neonates, the expression on HSC decreased with aging, and in mice older than 10 weeks, most of HSC are included in CD34-negative fraction. These results are useful for the further development of regenerative medicine, and the analysis of mammalian organogenesis.
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