Dextran sulfate and stromal cell derived factor-1 enhance the expression of CXCR4 and improve the homing efficiency of hematopoletic stem cells in bone marrow
| Project/Area Number |
14570780
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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 | Nippon Medical School |
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Principal Investigator |
FUKUNAGA Yoshitaka Nippon Medical School, Department of Pediatrics, Professor, 大学院・医学研究科, 教授 (50097036)
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| Co-Investigator(Kenkyū-buntansha) |
UEDA Takahiro Nippon Medical School, Department of Pediatrics, medical doctor, 医学部, 助手 (20322505)
MIGITA Makoto Nippon Medical School, Department of Pediatrics, Assistant Professor, 医学部, 講師 (50256963)
HAYAKAWA Jun Nippon Medical School, Department of Pediatrics, medical doctor
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Dextran Sulfate / SDF-1 / CXCR4 / Homing of HSCs / Dextran sulfate / CXCR4 / SDF1 / 遺伝子導入 |
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| Research Abstract |
Homing of hematopoietic stem cells (HSCs) in bone marrow (BM) is an important step of hematopoietic development and bone marrow repopulation. It is postulated that the circulating HSCs interact with BM endothelial cells, extravasate, and finally reach the specialized BM micrenvironment called "niches'. Although various kinds of chemokines, cytokines, and adhesion molecules supposed to be involved, the mechanism of HSC homing is not fully understood. Recent studies suggested that interaction of the chemokine receptor CXCR4 and its ligand, stromnal derived factor 1 (SDF-1) plays critical roles in multiple steps of HSC homing. In addition, it was reported that dextran sulfate (DEX) increased plasma levels of SDF1 and HSCs in mice and non-human primates. In this study, we examined the effects of preconditioning with SDF1 and DEX on the homing efficiency of HSCs during BM transplantation. SDF-1 (100ng/kg), DEX (100mg/kg), or PBS was injected into donor GFP transgenic mice 4 times for 4 cons
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ecutive days before harvesting BM cells. Quantitative RP-PCR analysis showed CXCR4 expression on GFP+BM cells was increased in both SDF-1 and DEX treated mice. DEX pretreatment also increased the levels of homing related molecules including MMP9, E-selectin, VEGF, VLA5, and LFA1 in BM cells harvested from the donor mice. Flow cytometry analysis demonstrated that the reconstitution efficiencies at 7 days after BM transplantation were significantly higher with BM cells from SDF-1 treated (45.1±10.1%) and DEX6 treated mice (72.3±7.1%) comnpored to control mice (35.2±1.6%)(n=3). The DEX mediated enhancement of reconstitution at an early stage was also observed in peripheral blood, thymus and spleen. However, the differences became not significant 30 days after BM transplantation. These results indicate that both SDF-1 and DEX are capable of enhancement of HSC homing SDF-1 may directly upregulate CXCR4 expression on HSCs, widle DEX appears to multiple functions including induction of SDF-1 and other molecules required for homing. Preconditioning with DEX may offer a novel clinical approach to improve homing and engraftment of HSCs. Less
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Report
(3 results)
Research Products
(2 results)
