1. Differential mobilization of subsets of progenitor cells from the bone marrow.
- Author
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Pitchford SC, Furze RC, Jones CP, Wengner AM, and Rankin SM
- Subjects
- Animals, Benzylamines, Bone Marrow Cells drug effects, Cell Cycle drug effects, Cell Shape drug effects, Chemokine CXCL12 metabolism, Chemotaxis drug effects, Cyclams, Cytokines administration & dosage, Cytokines pharmacology, Erythroid Precursor Cells cytology, Erythroid Precursor Cells drug effects, Erythroid Precursor Cells metabolism, Granulocyte Colony-Stimulating Factor pharmacology, Hematopoietic Stem Cells drug effects, Hematopoietic Stem Cells metabolism, Heterocyclic Compounds pharmacology, Mice, Mice, Inbred BALB C, Neutrophils cytology, Neutrophils drug effects, Receptors, CXCR4 antagonists & inhibitors, Receptors, CXCR4 metabolism, Stromal Cells cytology, Stromal Cells drug effects, Vascular Endothelial Growth Factor A pharmacology, Vascular Endothelial Growth Factor Receptor-1 antagonists & inhibitors, Bone Marrow Cells cytology, Hematopoietic Stem Cell Mobilization, Hematopoietic Stem Cells cytology
- Abstract
G-CSF stimulates mobilization of hematopoietic progenitor cells (HPCs) from bone marrow by disrupting the CXCR4/SDF-1alpha retention axis. We show here that distinct factors and mechanisms regulate the mobilization of endothelial (EPCs) and stromal progenitor cells (SPCs). Pretreatment of mice with VEGF did not disrupt the CXCR4/SDF-1alpha chemokine axis but stimulated entry of HPCs into the cell cycle via VEGFR1, reducing their migratory capacity in vitro and suppressing their mobilization in vivo. In contrast, VEGF pretreatment enhanced EPC mobilization via VEGFR2 in response to CXCR4 antagonism. Furthermore, SPC mobilization was detected when the CXCR4 antagonist was administered to mice pretreated with VEGF, but not G-CSF. Thus, differential mobilization of progenitor cell subsets is dependent upon the cytokine milieu that regulates cell retention and proliferation. These findings may inform studies investigating mechanisms that regulate progenitor cell recruitment in disease and can be exploited to provide efficacious stem cell therapy for tissue regeneration.
- Published
- 2009
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