Abstract
Background aims
Bone marrow (BM)-derived cells may repair cardiovascular injury but populations of interest circulate in small numbers. Cytokines such as granulocyte–colony-stimulating factor mobilize cells under investigation for this purpose, including CD133+ 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 CD34+ stem cells, on CD133+ 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). CD133+ and CD133+/VEGFR-2+ cells were measured by flow cytometry at baseline, then 4–6 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. CD133+ 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. CD133+/VEGFR-2+ 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
CD133+ 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.
Acknowledgments
This research was supported by the Intramural Research Programs of the National Heart, Lung and Blood Institute and the Clinical Center, National Institutes of Health.
Declaration of interest: No author has any conflict of interest related to this study.