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

Cytotherapy
Arnon BlumRichard O Cannon

Abstract

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. 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. 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 followi...Continue Reading

References

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