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

Cytotherapy. 2009;11(8):1016-9. doi: 10.3109/14653240903131640.


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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • AC133 Antigen
  • Adult
  • Antigens, CD / metabolism
  • Benzylamines
  • Blood Cell Count
  • Cardiovascular Diseases / therapy*
  • Cyclams
  • Female
  • Flow Cytometry
  • Glycoproteins / metabolism
  • Hematopoietic Stem Cell Mobilization*
  • Heterocyclic Compounds / pharmacology*
  • Humans
  • Male
  • Peptides / metabolism
  • Receptors, CXCR4 / antagonists & inhibitors*


  • AC133 Antigen
  • Antigens, CD
  • Benzylamines
  • Cyclams
  • Glycoproteins
  • Heterocyclic Compounds
  • PROM1 protein, human
  • Peptides
  • Receptors, CXCR4
  • plerixafor