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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3662-3667.
Prepublished online as a Blood First Edition Paper on August 15, 2006; DOI 10.1182/blood-2006-06-030577.


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Submitted June 21, 2006
Accepted July 18, 2006

Angiogenic cells can be rapidly mobilized and efficiently harvested from the blood following treatment with AMD3100

Rebecca M Shepherd, Benjamin J Capoccia, Steven M Devine, John DiPersio, Kathryn M Trinkaus, David Ingram, and Daniel C Link*

Washington University School of Medicine, Saint Louis, Missouri, USA
Ohio State University School of Medicine and Public Health, Ohio, USA
Herman B. Wells Center for Pediatric Research, Indiana Univesity School of Medicine, Indiana, USA

* Corresponding author; email: dlink{at}im.wustl.edu.

Circulating endothelial progenitor cells (EPC) are thought to contribute to angiogenesis following vascular injury, stimulating interest in their ability to mediate therapeutic angiogenesis. However, the number of EPC in the blood is low, limiting endogenous repair, and a method to rapidly mobilize EPC has not been reported. In this study, healthy donors were mobilized sequentially with the CXCR4 antagonist, AMD3100, and G-CSF. The number of EPC and circulating angiogenic cells (CAC) in blood and pheresis product was determined and the angiogenic capacity of each cell population assessed. Compared to baseline, treatment with AMD3100 or G-CSF increased the number of blood CAC 10.0± 4.4 and 8.8± 3.7-fold, respectively. The number of EPC in the blood increased 10.2± 3.3 and 21.8± 5.4-fold, respectively. On a per cell basis, CAC harvested from G-CSF mobilized blood displayed increased in vivo angiogenic potential compared with AMD3100 mobilized CAC. Mobilized EPC displayed a greater proliferative capacity than EPC isolated from baseline blood. Both CAC and EPC were efficiently harvested by leukapheresis. Cryopreserved CAC but not EPC retained functional activity after thawing. These data show that AMD3100 is a potent and rapid mobilizer of angiogenic cells and demonstrates the feasibility of obtaining and storing large numbers of angiogenic cells by leukapheresis.


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