Cdc42 inhibitor ML141 enhances G-CSF-induced hematopoietic stem and progenitor cell mobilization
Cdc42 inhibitor ML141 enhances G-CSF-induced hematopoietic stem and progenitor cell mobilization
复制标题
Cdc42 抑制剂 ML141 增强 G-CSF 诱导的造血干细胞和祖细胞动员
DOI：
10.1007/s12185-014-1690-z
复制
发表时间：
2015-01-01
影响因子：
2.1
通讯作者：
Xu, Kailin
中科院分区：
文献类型：
--
作者：
Chen, Chong;Song, Xuguang;Xu, Kailin
G-CSF is the most often used agent in clinical hematopoietic stem and progenitor cell (HSPC) mobilization. However, in about 10 % of patients, G-CSF does not efficiently mobilize HSPC in clinically sufficient amounts. Cdc42 activity is involved in HSPC mobilization. In the present study, we explore the impact of Cdc42 inhibitor ML141 on G-CSF-mediated HSPC mobilization in mice. We found that the use of ML141 alone only triggered modest HSPC mobilization effect in mice. However, combination of G-CSF and ML141 significantly promoted HPSC counts and colony forming units in peripheral blood, as compared to mice treated with G-CSF alone. ML141 did not significantly alter the levels of SDF-1 and MMP-9 in the bone marrow, when used alone or in combination with G-CSF. We also found that G-CSF administration significantly increases the level of GTP-bound Cdc42, but does not alter the expression of Cdc42 in the bone marrow. Our data indicate that the Cdc42 signal is a negative regulator in G-CSF-mediated HSPC mobilization, and that inhibition of the Cdc42 signal efficiently improves mobilization efficiency. These findings may provide a new strategy for efficient HSPC mobilization, especially in patients with poor G-CSF response.
