Efficacy of CXCR4 antagonist–based mobilization regimen. (A-C) Comparison of continuous infusion (cont. inf.) and bolus injection. The CXCR4 antagonists POL5551 (POL), AMD3100 (AMD), and ALT1188 (ALT) were administered to C57BL/6 mice as a single intraperitoneal (IP) injection (POL5551, 100 mg/kg; AMD3100, 20 mg/kg; ALT1188, 33 mg/kg) or as a continuous infusion for 2 weeks via subcutaneously implanted pumps (POL5551, 100 mg/kg per day; AMD3100, 20 mg/kg per day; ALT1188, 33 mg/kg per day). Peripheral blood (PB) was analyzed (at 3 hours after injection of bolus POL5551 and ALT1188, at 1 hour after injection of bolus AMD3100, at day 14 [d14] for all groups treated by continuous infusion) for (A) CFU-C/LSK, (B) LSK SLAM, and (C) white blood cell (WBC) concentration. Corresponding counts from age- and sex-matched healthy male mice injected with vehicle or sham-operated are shown as control (ctr.) mean ± standard error of the mean (SEM) (n = 5-10 mice for treated groups; n = 15 for control mice). (D) Pharmacokinetics. C57BL/6 mice were treated with a continuous infusion of POL5551 (50 mg/kg per day for 1 week). Plasma concentration of POL5551 (solid line) was analyzed at the indicated time points. Corresponding CFU-C numbers (dotted line) are shown for comparison. (E-F) Combination of CXCR4 and VLA4 blockade. At the end of treatment with continuous infusion of POL5551 as described in (A-C), mice were randomly assigned to receive either an IP bolus injection of AMD3100 (20 mg/kg) or the VLA4 antagonist CWHM-823 (3 mg/kg). One hour later, (E) CFU-C/LSK and (F) LSK SLAM numbers were quantified. CFU-C, LSK, and LSK SLAM counts obtained before the bolus treatment (ie, from corresponding POL5551 infusion–treated mice [A-C]) are shown for comparison (mean ± SEM; n = 5). ***P < .001; **P < .01; *P < .05. appr., approximately; n.s., not significant.