AMD3100 mobilizes hematopoietic stem cells with long-term repopulating capacity in nonhuman primates
AMD3100 mobilizes hematopoietic stem cells with long-term repopulating capacity in nonhuman primates
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DOI：
10.1182/blood-2005-09-3592
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发表时间：
2006-05-01
期刊：
影响因子：
20.3
通讯作者：
Hematti, P
中科院分区：
文献类型：
--
作者：
Larochelle, A;Krouse, A;Hematti, P
AMD3100是一种趋化因子受体CXCR4的双环拮抗剂，已被证明可以诱导小鼠、狗和人类的CD34（+）造血细胞的快速动员，为G-CSIF动员外周血造血干细胞提供了一种替代方法。在这项研究中，amd3100动员的CD34（+）细胞进行表型分析，用含有Neo (R)的逆转录病毒载体标记，随后移植到清髓恒河猴中。研究人员在移植后32个月，将转染AMD3100的CD34（+）细胞与Neo (R)基因标记的髓细胞和淋巴细胞进行移植，证明AMD3100能够动员真正的长期再生造血干细胞。与G- csf动员的CD34（+）细胞相比，amd3100动员的CD34（+）细胞更多地处于细胞周期的G期，更多的细胞表达CXCR4和VLA-4。使用amd3100动员的CD34（+）细胞获得的体内基因标记水平优于单独使用G-CSF动员的CD34（+）细胞获得的水平。综上所述，这些结果表明AMD3100动员的造血干细胞群与G-CSF动员的造血干细胞群具有不同的内在特征，表明AMD3100介导的造血干细胞动员机制与G-CSF介导的造血干细胞动员机制存在根本差异。因此，amd3100动员的CD34（+）细胞代表了临床干细胞移植和整合逆转录病毒载体的遗传操作的造血干细胞的替代来源。
AMD3100, a bicyclam antagonist of the chemokine receptor CXCR4, has been shown to induce rapid mobilization of CD34(+) hematopoietic cells in mice, dogs, and humans, offering an alternative to G-CSIF mobilization of peripheral-blood hematopoietic stem cells. In this study, AMD3100-mobilized CD34(+) cells were phenotypically analyzed, marked with Neo (R)-containing retroviral vectors, and subsequently transplanted into myeloablated rhesus macaques. We show engraftment of transduced AMD3100-mobilized CD34(+) cells with Neo (R) gene marked myeloid and lymphoid cells up to 32 months after transplantation, demonstrating the ability of AMD3100 to mobilize true long-term repopulating hematopoietic stem cells. More AMD3100-mobilized CD34(+) cells are in the G, phase of the cell cycle and more cells express CXCR4 and VLA-4 compared with G-CSF-mobilized CD34(+) cells. In vivo gene marking levels obtained with AMD3100-mobilized CD34(+) cells were better than those obtained using CD34(+) cells mobilized with G-CSF alone. Overall, these results indicate that AMD3100 mobilizes a population of hematopoietic stem cells with intrinsic characteristics different from those of hematopoietic stem cells mobilized with G-CSF, suggesting fundamental differences in the mechanism of AMD3100-mediated and G-CSF-mediated hematopoietic stem cell mobilization. Thus, AMD3100-mobilized CD34(+) cells represent an alternative source of hematopoietic stem cells for clinical stem cell transplantation and genetic manipulation with integrating retroviral vectors.