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

Circulation. 2004 Nov 23;110(21):3300-5. doi: 10.1161/01.CIR.0000147780.30124.CF. Epub 2004 Nov 8.


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.

Methods and 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benzylamines
  • Bone Marrow Cells / cytology
  • Bone Marrow Transplantation*
  • Cell Lineage
  • Cell Movement / physiology*
  • Chemokine CXCL12
  • Chemokines, CXC / biosynthesis
  • Chemokines, CXC / blood
  • Chemokines, CXC / genetics
  • Chemokines, CXC / physiology*
  • Cyclams
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genetic Therapy
  • Heterocyclic Compounds / pharmacology
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Intercellular Adhesion Molecule-1 / genetics
  • Matrix Metalloproteinase 9 / biosynthesis
  • Matrix Metalloproteinase 9 / genetics
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Myocardial Infarction / genetics
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / physiopathology*
  • Myocardial Infarction / therapy
  • Myocardium / pathology
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / physiology*
  • Recombinant Fusion Proteins / physiology
  • Stem Cell Transplantation*
  • Stem Cells / cytology*
  • Transduction, Genetic
  • Vascular Cell Adhesion Molecule-1 / biosynthesis
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / genetics


  • Benzylamines
  • Chemokine CXCL12
  • Chemokines, CXC
  • Cxcl12 protein, mouse
  • Cyclams
  • Heterocyclic Compounds
  • Receptors, CXCR4
  • Recombinant Fusion Proteins
  • Vascular Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A
  • Intercellular Adhesion Molecule-1
  • Matrix Metalloproteinase 9
  • plerixafor