G-CSF treatment after myocardial infarction: impact on bone marrow-derived vs cardiac progenitor cells.
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.
Brunner
Stefan
S
Ludwig-Maximilians-University, Klinikum Grosshadern, Medical Department I, Munich, Germany.
Huber
Bruno C
BC
Fischer
Rebekka
R
Groebner
Michael
M
Hacker
Marcus
M
David
Robert
R
Zaruba
Marc-Michael
MM
Vallaster
Marcus
M
Rischpler
Christoph
C
Wilke
Andrea
A
Gerbitz
Armin
A
Franz
Wolfgang-Michael
WM
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
D017931:DNA Primers; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; D049452:Green Fluorescent Proteins