title: G-CSF treatment after myocardial infarction: impact on bone marrow-derived vs cardiac progenitor cells.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Ludwig-Maximilians-University, Klinikum Grosshadern, Medical Department I, Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Brunner
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Huber
authors.forename: Rebekka
authors.initials: R
authors.lastname: Fischer
authors.forename: Michael
authors.initials: M
authors.lastname: Groebner
authors.forename: Marcus
authors.initials: M
authors.lastname: Hacker
authors.forename: Robert
authors.initials: R
authors.lastname: David
authors.forename: Marc-Michael
authors.initials: MM
authors.lastname: Zaruba
authors.forename: Marcus
authors.initials: M
authors.lastname: Vallaster
authors.forename: Christoph
authors.initials: C
authors.lastname: Rischpler
authors.forename: Andrea
authors.initials: A
authors.lastname: Wilke
authors.forename: Armin
authors.initials: A
authors.lastname: Gerbitz
authors.forename: Wolfgang-Michael
authors.initials: WM
authors.lastname: Franz
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D017931:DNA Primers; D004195:Disease Models, Animal; D005434:Flow Cytometry; D017930:Genes, Reporter; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D019650:Hematopoietic Stem Cell Mobilization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000601:surgery*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; D049452:Green Fluorescent Proteins