G-CSF treatment after myocardial infarction: impact on bone marrow-derived vs cardiac progenitor cells

Exp Hematol. 2008 Jun;36(6):695-702. doi: 10.1016/j.exphem.2008.01.011. Epub 2008 Mar 17.


Objective: Besides its classical function in the field of autologous and allogenic stem cell transplantation, granulocyte colony-stimulating factor (G-CSF) was shown to have protective effects after myocardial infarction (MI) by mobilization of bone marrow-derived progenitor cells (BMCs) and in addition by activation of multiple signaling pathways. In the present study, we focused on the impact of G-CSF on migration of BMCs and the impact on resident cardiac cells after MI.

Materials and methods: Mice (C57BL/6J) were sublethally irradiated, and BM from green fluorescent protein (GFP)-transgenic mice was transplanted. Coronary artery ligation was performed 10 weeks later. G-CSF (100 microg/kg) was daily injected for 6 days. Subpopulations of enhanced GFP(+) cells in peripheral blood, bone marrow, and heart were characterized by flow cytometry. Growth factor expression in the heart was analyzed by quantitative real-time polymerase chain reaction. Perfusion was investigated in vivo by gated single photon emission computed tomography (SPECT).

Results: G-CSF-treated animals revealed a reduced migration of c-kit(+) and CXCR-4(+) BMCs associated with decreased expression levels of the corresponding growth factors, namely stem cell factor and stromal-derived factor-1 alpha in ischemic myocardium. In contrast, the number of resident cardiac Sca-1(+) cells was significantly increased. However, SPECT-perfusion showed no differences in infarct size between G-CSF-treated and control animals 6 days after MI.

Conclusion: Our study shows that G-CSF treatment after MI reduces migration capacity of BMCs into ischemic tissue, but increases the number of resident cardiac cells. To optimize homing capacity a combination of G-CSF with other agents may optimize cytokine therapy after MI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Transplantation / methods*
  • DNA Primers
  • Disease Models, Animal
  • Flow Cytometry
  • Genes, Reporter
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Green Fluorescent Proteins / analysis
  • Green Fluorescent Proteins / genetics
  • Hematopoietic Stem Cell Mobilization
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / surgery*
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction


  • DNA Primers
  • RNA, Messenger
  • Granulocyte Colony-Stimulating Factor
  • Green Fluorescent Proteins