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PMID: 17416737 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural

The chemokine GRObeta mobilizes early hematopoietic stem cells characterized by enhanced homing and engraftment.

Blood ·Vol. 110 ·No. 3 ·2007-08-01 ·Pages 860-9

Fukuda S, Bian H, King AG, Pelus LM

Abstract

Mobilized peripheral blood hematopoietic stem cells (PBSCs) demonstrate accelerated engraftment compared with bone marrow; however, mechanisms responsible for enhanced engraftment remain unknown. PBSCs mobilized by GRObeta (GRObeta(Delta4)/CXCL2(Delta4)) or the combination of GRObeta(Delta4) plus granulocyte colony-stimulating factor (G-CSF) restore neutrophil and platelet recovery faster than G-CSF-mobilized PBSCs. To determine mechanisms responsible for faster hematopoietic recovery, we characterized immunophenotype and function of the GRObeta-mobilized grafts. PBSCs mobilized by GRObeta(Delta4) alone or with G-CSF contained significantly more Sca-1(+)-c-kit(+)-lineage(-) (SKL) cells and more primitive CD34(-)-SKL cells compared with cells mobilized by G-CSF and demonstrated superior competitive long-term repopulation activity, which continued to increase in secondary and tertiary recipients. GRObeta(Delta4)-mobilized SKL cells adhered better to VCAM-1(+) endothelial cells compared with G-CSF-mobilized cells. GRObeta(Delta4)-mobilized PBSCs did not migrate well to the chemokine stromal derived factor (SDF)-1alpha in vitro that was associated with higher CD26 expression. However, GRObeta(Delta4)-mobilized SKL and c-Kit(+) lineage(-) (KL) cells homed more efficiently to marrow in vivo, which was not affected by selective CXCR4 and CD26 antagonists. These data suggest that GRObeta(Delta4)-mobilized PBSCs 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 GRObeta(Delta4)-mobilized cells is less dependent on the SDF-1alpha/CXCR4 axis.

MeSH Terms
Animals Antigens, CD34/metabolism Antigens, Ly/metabolism Cell Adhesion/drug effects Cell Movement/drug effects Chemokine CXCL1 Chemokine CXCL12 Chemokines, CXC/deficiency,metabolism,pharmacology Dipeptidyl Peptidase 4/biosynthesis Endothelial Cells/metabolism Female Gene Expression Regulation/drug effects Graft Survival/drug effects Granulocyte Colony-Stimulating Factor/pharmacology Hematopoiesis/drug effects Hematopoietic Stem Cell Mobilization Hematopoietic Stem Cells/metabolism Membrane Proteins/metabolism Mice Mice, Inbred BALB C Mice, Knockout Peripheral Blood Stem Cell Transplantation Proto-Oncogene Proteins c-kit/metabolism Receptors, CXCR4/metabolism Recovery of Function/drug effects Transplantation, Homologous Vascular Cell Adhesion Molecule-1/metabolism
Chemicals
Antigens, CD34 Antigens, Ly CXCR4 protein, mouse Chemokine CXCL1 Chemokine CXCL12 Chemokines, CXC Cxcl1 protein, mouse Cxcl12 protein, mouse Ly6a protein, mouse Membrane Proteins Receptors, CXCR4 Vascular Cell Adhesion Molecule-1 Granulocyte Colony-Stimulating Factor Proto-Oncogene Proteins c-kit Dipeptidyl Peptidase 4
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Fukuda Seiji
Department of Microbiology and Immunology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Bian Huimin
King Andrew G
Pelus Louis M
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Article Info
Journal
Blood
Abbr.
Blood
ISSN
0006-4971
DOI
10.1182/blood-2006-06-031401
Published
2007-08-01
Epub
2007-00-06
Pages
860-9
Language
English
Region
United States
NLM ID
7603509
PMCID
PMC1924764
Subset
IM
Grants
NHLBI NIH HHS · R01 HL069669 · United States
NHLBI NIH HHS · R01 HL079654 · United States
NHLBI NIH HHS · HL 079654 · United States
NHLBI NIH HHS · HL 69669 · United States
External Links
PubMed source DOI: 10.1182/blood-2006-06-031401 PMC Full Text View journal details
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