Angiogenic cells can be rapidly mobilized and efficiently harvested from the blood following treatment with AMD3100.
Circulating endothelial progenitor cells (EPCs) are thought to contribute to angiogenesis following vascular injury, stimulating interest in their ability to mediate therapeutic angiogenesis. However, the number of EPCs in the blood is low, limiting endogenous repair, and a method to rapidly mobilize EPCs has not been reported. In this study, healthy donors were mobilized sequentially with the CXCR4 antagonist, AMD3100, and G-CSF. The number of EPCs and circulating angiogenic cells (CACs) in the blood and pheresis product was determined and the angiogenic capacity of each cell population assessed. Compared with baseline, treatment with AMD3100 or G-CSF increased the number of blood CACs 10.0-fold +/- 4.4-fold and 8.8-fold +/- 3.7-fold, respectively. The number of EPCs in the blood increased 10.2-fold +/- 3.3-fold and 21.8-fold +/- 5.4-fold, respectively. On a percell basis, CACs harvested from G-CSF-mobilized blood displayed increased in vivo angiogenic potential compared with AMD3100-mobilized CACs. Mobilized EPCs displayed a greater proliferative capacity than EPCs isolated from baseline blood. Both CACs and EPCs were efficiently harvested by leukapheresis. Cryopreserved CACs but not EPCs retained functional activity after thawing. These data show that AMD3100 is a potent and rapid mobilizer of angiogenic cells and demonstrate the feasibility of obtaining and storing large numbers of angiogenic cells by leukapheresis.
Shepherd
Rebecca M
RM
Division of Oncology, Department of Medicine, 660 S Euclid Ave, Campus Box 8007, Saint Louis, MO 63110, USA.
Capoccia
Benjamin J
BJ
Devine
Steven M
SM
Dipersio
John
J
Trinkaus
Kathryn M
KM
Ingram
David
D
Link
Daniel C
DC
D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001596:Benzylamines; D001782:Blood Donors; D049109:Cell Proliferation; D015925:Cryopreservation / Q000379:methods; D000080027:Cyclams; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D019650:Hematopoietic Stem Cell Mobilization / Q000009:adverse effects / Q000379:methods; D006571:Heterocyclic Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007279:Injections, Subcutaneous; D007937:Leukapheresis / Q000379:methods; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018919:Neovascularization, Physiologic / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology
D019380:Anti-HIV Agents; D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor