Differential mobilization of subsets of progenitor cells from the bone marrow.
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.
Pitchford
Simon C
SC
Leukocyte Biology Section, National Heart and Lung Institute, Imperial College, London SW7 2AZ, UK.
Furze
Rebecca C
RC
Jones
Carla P
CP
Wengner
Antje M
AM
Rankin
Sara M
SM
D000818:Animals; D001596:Benzylamines; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D000080027:Cyclams; D016207:Cytokines / Q000008:administration & dosage / Q000494:pharmacology; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors
D001596:Benzylamines; D054377:Chemokine CXCL12; D000080027:Cyclams; D016207:Cytokines; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; C088327:plerixafor