期刊
BLOOD
卷 115, 期 3, 页码 443-452出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2009-05-222711
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资金
- CEA
- La Ligue de Paris contre le Cancer [RS 07/75-20]
- ARC [3527]
- ANR [NT05-2-44232, 06-TecScan-019-04, 06-EMPB-002]
- Inserm
- CEA/DSV
- European Molecular Imaging Laboratories European Network of Excellence
- European Union [LSH-2004-503569]
Few techniques are available to characterize in vivo the early cellular dynamics of long-term reconstitution of hematopoiesis after transplantation of hematopoietic stem cells (HSCs) after lethal irradiation. Using a fiber-optic imaging system, we track the early steps of in vivo recruitment and proliferation of Lin(-)Sca-1(+)c-Kit(+)CD34(-) (LSKCD34(-)) HSCs highly enriched in HSCs and transplanted into lethally irradiated mice. Recruitment of the transplanted LSKCD34(-) hematopoietic cells first occurs in the femoral head and is continuous during 24 hours. Quantification of the fluorescence emitted by the transplanted hematopoietic cells shows that proliferation of LSKCD34(-) hematopoietic cells in the femoral head was potent 3 days after transplantation. Using a development of this fiber-optic imaging system, we show that the transplanted LSKCD34(-) hematopoietic cells are associated with vascularized structures as early as 5 hours after transplantation. This early association is dependent on reactive oxygen species (ROS) partly through the regulation of vascular cell adhesion molecule-1 expression on endothelial cells and is followed by a ROS-dependent proliferation of LSKCD34(-) hematopoietic cells. This new in vivo imaging technique permits the observation of the early steps of hematopoietic reconstitution by HSCs in long bones and shows a new role of ROS in the recruitment of HSCs by bone marrow endothelial cells. (Blood. 2010; 115: 443-452)
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