Targeted antagonism of CXCR4 mobilizes progenitor cells under investigation for cardiovascular disease

Background aims Bone marrow (BM)-derived cells may repair cardiovascular injury but populations of interest circulate in small numbers. Cytokines such as granulocytecolony-stimulating factor mobilize cells under investigation for this purpose, including CD133¹ but require injections over multiple days and may promote inflammation. The purpose of this study was to evaluate the effects of a novel CXCR4 inhibitor (plerixafor), previously shown to mobilize CD34¹ stem cells, on CD133¹ mobilization and markers of inflammation. Methods Healthy subjects received a single subcutaneous injection of plerixafor in escalating doses: 240 mcg/kg (n 3), 320 mcg/kg (n 5) and 400 mcg/kg (n 7). CD133¹ and CD133¹/VEGFR-2¹ cells were measured by flow cytometry at baseline, then 46 h following plerixafor injection. Markers of inflammation in serum were measured at baseline, then again 10 h following injection of the 400 mcg/kg dose. Results Across all doses, white blood cells increased on average three-fold from baseline values. CD133¹ cells increased on average 24-fold (from 616 ± 141 cells/mL to 14 713 ± 4423 cells/mL, P 0.0064) without clear evidence of a dose effect. CD133¹/VEGFR-2¹ cells ranged from 0 to 20 cells/mL at baseline and from 0 to 124 cells/mL following plerixafor administration, although the rarity of these cells precluded a statistical analysis of this population. C-reactive protein and serum amyloid type A were not increased after the 400 mcg/kg dose. Pro-inflammatory cytokine levels were undetectable before and after plerixafor, except for macrophage inflammatory protein-1 beta, which increased slightly but significantly after the 400 mcg/kg dose of plerixafor (P 0.0156). Conclusions CD133¹ cells are mobilized into the circulation following a single injection of the CXCR4 antagonist plerixafor, without clear evidence for systemic activation of inflammation. This effect may be of importance in cell-based approaches for treating cardiovascular diseases.