In vivo cellular imaging pinpoints the role of reactive oxygen species in the early steps of adult hematopoietic reconstitution
In vivo cellular imaging pinpoints the role of reactive oxygen species in the early steps of adult hematopoietic reconstitution
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DOI：
10.1182/blood-2009-05-222711
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发表时间：
2010-01-21
期刊：
影响因子：
20.3
通讯作者：
Romeo, Paul-Henri
中科院分区：
文献类型：
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作者：
Lewandowski, Daniel;Barroca, Vilma;Romeo, Paul-Henri
很少有技术可以在体内表征致死照射后造血干细胞移植后长期造血重建的早期细胞动力学。利用光纤成像系统，我们跟踪了在体内募集和增殖的早期步骤，LIN(-)SCA-1(+)c-Kit(+)CD34(-)(LSKCD34(-))HSCs高度富含HSCs并移植到致死照射的小鼠体内。移植的LSKCD34(-)造血细胞的募集首先发生在股骨头，并在24小时内持续。移植后3天LSKCD34(-)造血细胞在股骨头内的增殖能力较强。利用这种光纤成像系统的发展，我们发现移植的LSKCD34(-)造血细胞早在移植后5小时就与血管结构相关。这种早期的关联部分依赖于活性氧(ROS)，部分是通过调节内皮细胞上血管细胞黏附分子-1的表达，随后是LSKCD34(-)造血细胞依赖ROS的增殖。这一新的体内成像技术可以观察长骨中造血干细胞重建的早期步骤，并显示了ROS在骨髓内皮细胞募集造血干细胞中的新作用。(血。2010；115：443-452)
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)