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

Arnon Blum, Richard W. Childs, Aleah Smith, Sushmitha Patibandla, Gloria Zalos, Leigh Samsel, J. Philip McCoy, Gary Calandra, Gyorgy Csako, Richard O. Cannon

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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.

Original languageEnglish
Pages (from-to)1016-1019
Number of pages4
Issue number8
StatePublished - 2009
Externally publishedYes

Bibliographical note

Funding Information:
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 .


  • CXCR4 antagonism
  • Cardiovascular disease
  • Heart disease
  • Infl ammation
  • Progenitor cells
  • Vascular repair.


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