G-CSF stimulates mobilization of hematopoietic progenitor cells (HPCs) from bone marrownormally by disrupting the CXCR4/SDF-1 alpha retention axis. We display right here that distinct variables and mechanisms regulate the mobilization of endothelial (EPCs) and stromal progenitor cells (SPCs). Pretreatment of mice with VEGF did not disrupt the CXCR4/SDF-1 alpha chemokine HSP90 axis but stimulated entry of HPCs to the cell cycle via VEGFR1, reducing their migratory capacity in vitro and suppressing their mobilization in vivo. In contrast, VEGF pretreatment enhanced EPC mobilization via VEGFIR2 in response to CXCR4 antagonism. On top of that, SPC mobilization was detected once the CXCR4 antagonist was administered to mice pretreated with VEGF, but not G-CSF. So, differential mobilization of progenitor cell subsets is dependent on the cytokine milieu that regulates cell retention and proliferation. These findings may well inform scientific studies investigating mechanisms that regulate progenitor cell recruitment in disease and can be exploited to provide efficacious stem cell therapy for tissue regeneration.