Small molecule Me6TREN mobilizes hematopoietic stem/progenitor cells by activating MMP-9 expression and disrupting SDF-1/CXCR4 axis
Small molecule Me6TREN mobilizes hematopoietic stem/progenitor cells by activating MMP-9 expression and disrupting SDF-1/CXCR4 axis
复制标题
小分子 Me6TREN 通过激活 MMP-9 表达并破坏 SDF-1/CXCR4 轴来动员造血干/祖细胞
DOI：
10.1182/blood-2013-04-498535
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发表时间：
2014-01-16
期刊：
影响因子：
20.3
通讯作者：
Pei, Xuetao
中科院分区：
文献类型：
--
作者：
Zhang, Jing;Ren, Xiangliang;Pei, Xuetao
动员造血干细胞和祖细胞（HSPC）从骨髓进入血液循环已被广泛用于造血移植。然而，目前的细胞因子或小分子刺激的HSPC动员方法远不能令人满意。需要新的动员剂来增加外周血中干细胞的数量，以有效地重建造血。在这里，我们报告说，分子Me 6 TREN（Me 6）可以诱导造血祖细胞的快速动员，Me 6表现出更显着的效果比粒细胞集落刺激因子（G-CSF）或AMD 3100。Me 6还动员了长期的再增殖细胞，这些细胞在初次和二次移植受体中以多谱系方式成功移植和扩增。在机制上，Me 6抑制SDF-1 α诱导的小鼠和人造血细胞的迁移和VLA-4介导的粘附。Me 6似乎通过激活MMP-9表达和破坏SDF-1 α/CXCR 4轴来动员HSPC。因此，Me 6有可能成为一种新的高效动员HSPCs的药物。
Mobilization of hematopoietic stem and progenitor cells (HSPCs) from bone marrow into the blood circulation has been widely used for hematopoietic transplantation. However, the current methods of cytokine- or small-molecule-stimulated HSPC mobilization are far from satisfactory. New mobilizing agents are needed to increase the number of stem cells in peripheral blood for effective reconstitution of hematopoiesis. Here, we report that the molecule Me6TREN (Me6) can induce rapid mobilization of hematopoietic progenitor cells and that Me6 exhibits more significant effects than granulocyte colony-stimulating factor (G-CSF) or AMD3100. Me6 also mobilizes long-term repopulating cells, which successfully engraft and expand in a multilineage fashion in primary and secondary transplant recipients. Mechanistically, Me6 inhibits both the SDF-1 alpha-induced migration and VLA-4-mediated adhesion of mouse and human hematopoietic cells. Me6 appears to mobilize HSPCs by activating MMP-9 expression and disrupting the SDF-1 alpha/CXCR4 axis. Therefore, Me6 may become a new potent and efficacious mobilizing agent of HSPCs.