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Cdc42 inhibitor ML141 enhances G-CSF-induced hematopoietic stem and progenitor cell mobilization.
- Source :
- International Journal of Hematology; Jan2015, Vol. 101 Issue 1, p5-12, 8p
- Publication Year :
- 2015
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09255710
- Volume :
- 101
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- International Journal of Hematology
- Publication Type :
- Academic Journal
- Accession number :
- 100318889
- Full Text :
- https://doi.org/10.1007/s12185-014-1690-z