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Blood, 1 August 2007, Vol. 110, No. 3, pp. 860-869.
Prepublished online as a Blood First Edition Paper on April 6, 2007; DOI 10.1182/blood-2006-06-031401.
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Submitted June 26, 2006
Accepted April 3, 2007
The chemokine GRO mobilizes early hematopoietic stem cells characterized by enhanced homing and engraftment
Seiji Fukuda, Huimin Bian, Andrew G King, and Louis M. Pelus*
Dept Microbiology & Immunology, & Walther Oncology Center, Indiana University School of Medicine, & the Walther Cancer Institute, Indianapolis, IN, United States
Microbial, Musculoskeletal and Proliferative Diseases Center, GlaxoSmithKline, Collegeville, PA, United States
* Corresponding author; email: lpelus{at}iupui.edu.
Mobilized peripheral blood hematopoietic stem cells (PBSC) demonstrate accelerated engraftment compared to bone marrow; however, mechanisms responsible for enhanced engraftment remain unknown. PBSC mobilized by GRO (GRO 4/CXCL2 4) or the combination of GRO 4 plus G-CSF restore neutrophil and platelet recovery faster than G-CSF-mobilized PBSC. To determine mechanisms responsible for faster hematopoietic recovery, we characterized immunophenotype and function of the GRO -mobilized grafts. PBSC mobilized by GRO 4 alone or with G-CSF contained significantly more Sca-1+-c-kit+-lineage- (SKL) cells and more primitive CD34neg-SKL cells compared to cells mobilized by G-CSF and demonstrated superior competitive long-term repopulation activity, which continued to increase in secondary and tertiary recipients. GRO 4-mobilized SKL cells adhered better to VCAM-1pos endothelial cells compared to G-CSF-mobilized cells. GRO 4-mobilized PBSC did not migrate well to SDF-1 in vitro that was associated with higher CD26 expression. However, GRO 4-mobilized SKL and KL cells homed more efficiently to marrow in vivo, which was not affected by selective CXCR4 and CD26 antagonists. These data suggest that GRO 4-mobilized PBSC are superior in reconstituting long-term hematopoiesis, which results from differential mobilization of early stem cells with enhanced homing and long-term repopulating capacity. In addition, homing and engraftment of GRO 4-mobilized cells is less dependent on the SDF-1 /CXCR4 axis.

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