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Glycosaminoglycan mimetics-induced mobilization of hematopoietic progenitors and stem cells into mouse peripheral blood: structure/function insights.
MedLine Citation:
PMID:  19539688     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Glycosaminoglycans (GAG) are major components of bone marrow extracellular matrix because they have the property to interact with cells and growth factors in hematopoietic niches. In this study, we investigated the effect of two different chemically defined GAG mimetics on mobilization of hematopoietic stem and progenitor cells (HSPCs) in mice peripheral blood. MATERIALS AND METHODS: Mobilization was achieved by intraperitoneal injection of GAG mimetics. Mobilized cells were characterized phenotypically by reverse transcription polymerase chain reaction and fluorescence-activated cell sorting analysis and functionally by colony-forming cell, cobblestone area-forming cell and long-term culture-initiating cell assays in vitro. Radioprotection assays were performed to confirm the functionality of primitive hematopoietic cells in vivo. Involvement of stromal-derived factor-1 (SDF-1) and matrix metalloproteinase-9 (MMP-9) were investigated. RESULTS: GAG mimetics treatment induces hyperleukocytosis and mobilization of HSPC. They synergize with the effects of granulocyte colony-stimulating factor or AMD3100 on hematopoietic progenitors mobilization. Reconstitution of lethally irradiated recipient mice with peripheral blood mononuclear cells from GAG mimetic-treated donor mice improves engraftment and survival. BiAcore studies indicate that the mimetics interact directly with SDF-1. In addition, GAG mimetics-induced mobilization is associated with increased levels of pro- and active MMP-9 from bone marrow cells and increased level of SDF-1 in peripheral blood. Finally, mobilization is partially inhibited by co-injection with anti-SDF-1 antibody. CONCLUSION: This study demonstrates that GAG mimetics induce efficient mobilization of HSPCs, associated with an activation of pro-MMP-9 and a modification in the SDF-1 concentration gradient between bone marrow and peripheral blood. We suggest that structural features of GAGs can modify the nature of mobilized cells.
Patricia Albanese; Danielle Caruelle; Guilhem Frescaline; Jean Delbé; Laurence Petit-Cocault; Eric Huet; Nathalie Charnaux; Georges Uzan; Dulce Papy-Garcia; José Courty
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Publication Detail:
Type:  Journal Article     Date:  2009-06-17
Journal Detail:
Title:  Experimental hematology     Volume:  37     ISSN:  1873-2399     ISO Abbreviation:  Exp. Hematol.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-14     Completed Date:  2009-09-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0402313     Medline TA:  Exp Hematol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1072-83     Citation Subset:  IM    
CNRS UMR 7149, Laboratoire CRRET, Croissance Cellulaire, Réparation et Régénération Tissulaire, Créteil, France.
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MeSH Terms
Anti-HIV Agents / agonists,  pharmacology
Biomimetic Materials / pharmacology*
Bone Marrow / metabolism
Chemokine CXCL12 / blood*
Drug Synergism
Glycosaminoglycans / agonists,  pharmacology*
Graft Survival / drug effects
Granulocyte-Macrophage Colony-Stimulating Factor / agonists,  pharmacology
Hematopoietic Stem Cell Mobilization / methods*
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells / cytology*,  metabolism
Heterocyclic Compounds / agonists,  pharmacology
Matrix Metalloproteinase 9 / blood*
Structure-Activity Relationship
Transplantation, Homologous
Reg. No./Substance:
0/Anti-HIV Agents; 0/Chemokine CXCL12; 0/Cxcl12 protein, mouse; 0/Glycosaminoglycans; 0/Heterocyclic Compounds; 155148-31-5/JM 3100; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor; EC 3.4.24.-/Mmp9 protein, mouse; EC Metalloproteinase 9

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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