title: Stromal cell-derived factor-1alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury.
abstract: BACKGROUND
  After myocardial infarction (MI), bone marrow-derived cells (BMDCs) are found within the myocardium. The mechanisms determining BMDC recruitment to the heart remain unclear. We investigated the role of stromal cell-derived factor-1alpha (SDF-1) in this process.
  
  
  RESULTS
  MI produced in mice by coronary ligation induced SDF-1 mRNA and protein expression in the infarct and border zone and decreased serum SDF-1 levels. By quantitative polymerase chain reaction, 48 hours after intravenous infusion of donor-lineage BMDCs, there were 80.5+/-15.6% more BDMCs in infarcted hearts compared with sham-operated controls (P<0.01). Administration of AMD3100, which specifically blocks binding of SDF-1 to its endogenous receptor CXCR4, diminished BMDC recruitment after MI by 64.2+/-5.5% (P<0.05), strongly suggesting a requirement for SDF-1 in BMDC recruitment to the infarcted heart. Forced expression of SDF-1 in the heart by adenoviral gene delivery 48 hours after MI doubled BMDC recruitment over MI alone (P<0.001) but did not enhance recruitment in the absence of MI, suggesting that SDF-1 can augment, but is not singularly sufficient for, BDMC recruitment to the heart. Gene expression analysis after MI revealed increased levels of several genes in addition to SDF-1, including those for vascular endothelial growth factor, matrix metalloproteinase-9, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, which might act in concert with SDF-1 to recruit BMDCs to the injured heart.
  
  
  CONCLUSIONS
  SDF-1/CXCR4 interactions play a crucial role in the recruitment of BMDCs to the heart after MI and can further increase homing in the presence, but not in the absence, of injury.
authors.affiliation: Department of Cardiology, Yale University Medical School, New Haven, Conn, USA.
authors.forename: J Dawn
authors.initials: JD
authors.lastname: Abbott
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Dingang
authors.initials: D
authors.lastname: Liu
authors.forename: Reed
authors.initials: R
authors.lastname: Hickey
authors.forename: Diane S
authors.initials: DS
authors.lastname: Krause
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Giordano
mesh_terms: D000818:Animals; D001596:Benzylamines; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D019070:Cell Lineage; D002465:Cell Movement / Q000502:physiology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology*; D000080027:Cyclams; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D006571:Heterocyclic Compounds / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D009206:Myocardium / Q000473:pathology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D014161:Transduction, Genetic; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: D001596:Benzylamines; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D011993:Recombinant Fusion Proteins; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; D020780:Matrix Metalloproteinase 9; C088327:plerixafor