Crucial role of SDF-1/CXCR4 interaction in the recruitment of transplanted dermal multipotent cells to sublethally irradiated bone marrow.
Crucial role of SDF-1/CXCR4 interaction in the recruitment of transplanted dermal multipotent cells to sublethally irradiated bone marrow.
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DOI：
10.1269/jrr.0531
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发表时间：
2006-09
影响因子：
2
通讯作者：
Zhaowen Zong;T. Cheng;Yong-ping Su;X. Ran;Nan Li;G. Ai;Hui Xu
中科院分区：
文献类型：
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作者：
Zhaowen Zong;T. Cheng;Yong-ping Su;X. Ran;Nan Li;G. Ai;Hui Xu
我们前期的研究表明，真皮多能细胞（dermal multipotent cells，DMCs）可移植到亚致死剂量照射后的大鼠骨髓中，并促进全身移植后造血功能的恢复，但DMCs向辐射损伤骨髓募集的机制尚不清楚。在本研究中，我们研究了基质细胞衍生因子-1（SDF-1）/CXCR 4相互作用在这一过程中的作用。分离雄性DMCs并将其移植到雌性大鼠体内，采用Y染色体性别决定区实时荧光定量TaqMan聚合酶链反应（RT-PCR）技术，发现亚致死剂量照射后大鼠骨髓中DMCs的数量比正常大鼠增加约3倍（P < 0.01）。在移植前用AMD 3100孵育DMC，其特异性阻断SDF-1与其内源性受体CXCR 4的结合，使DMC向损伤BM的募集减少57.2 +/- 5.5%（P < 0.05）。体外实验表明，照射后大鼠骨髓提取物对DMCs有较强的趋化作用，但与AMD 3100预孵育后，其趋化作用明显减弱（P < 0.05）。这些数据表明，移植的DMCs更频繁地被招募到辐射损伤的BM比正常BM和SDF-1/CXCR 4的相互作用在这个过程中发挥了重要作用。
Our previous study indicated that dermal multipotent cells (DMCs) could engraft into bone morrow (BM) of rats with sublethal irradiation and promote hematopoietic recovery after being transplanted systemically, but the mechanisms determining the recruitment of DMCs to the irradiation injured BM remain unclear. In the present study, we investigated the role of stromal cellderived factor-1 (SDF-1)/CXCR4 interaction in this process. Male DMCs were isolated and transplanted into female rats systemically, and by employing quantitative real-time TaqMan polymerase chain reaction for the sex-determining region of Y chromosome, it was found that the amount of DMCs in BM of rats with sublethal irradiation was about 3 times more than that of normal rats (P < 0.01). Incubation of DMCs with AMD3100 before transplantation, which specifically blocks binding of SDF-1 to its endogenous receptor CXCR4, diminished recruitment of DMCs to the injured BM by 57.2 +/- 5.5% (P < 0.05). In addition, it was confirmed that the expression of SDF-1 in injured BM was up-regulated when compared with that in normal BM, and in vitro analysis revealed that BM extracts from irradiated rats had a strong chemotactic effect on DMCs, which decreased significantly when DMCs were pre-incubated with AMD3100 (P < 0.05). These data suggest that transplanted DMCs were recruited more frequently to irradiation-injured BM than normal BM and the interactions of SDF-1/CXCR4 played an important role in this process.