Effects of granulocyte-colony-stimulating factor on progenitor cell mobilization and heart perfusion and function in normal mice.
OBJECTIVE
Mobilization of stem cells and progenitor cells from the bone marrow (BM) into the peripheral blood (PB) by granulocyte-colony-stimulating factor (G-CSF) is being investigated for cardiac regeneration in ischemic heart disease. However, hematopoietic (HPC), mesenchymal (MPC) and endothelial (EPC) progenitor mobilization have not been optimized and the effect of G-CSF on myocardial perfusion and cardiac function in a normal heart has never been studied.


METHODS
Normal mice were injected daily for 1-10 days with subcutaneous recombinant human G-CSF. PB and BM were evaluated for HPC and EPC by flow cytometry and HPC and MPC by hematopoietic (CFU-GM) and mesenchymal (CFU-F) colony assays. Echocardiography, microSPECT imaging, cardiac catheterization and immunohistochemistry were performed in mice treated for 10 days.


RESULTS
HPC and CFU-GM in PB peaked after 2 days, CFU-F after 4 days and EPC after 3 days. Thereafter, while HPC temporally decreased before showing a second peak, EPC remained detectable only at low levels. In BM, hematopoietic stem cells (HSC) and CFU-GM did not increase much overall but peaked twice on days 2 and 7. EPC (peak on day 7) production increased in the BM, but CFU-F formation declined considerably after day 2. G-CSF enhanced myocardial perfusion and vascularization but impaired hemodynamic performance of the heart through apparently increased ventricular wall rigidity.


CONCLUSIONS
G-CSF induces the mobilization of HPC, EPC and CFU-F progenitors in PB according to very different patterns, and has a significant impact on perfusion and function of the normal heart.
Giga-Research, Hematology Unit, University of Liège, Liège, Belgium.
Marie
M
Delgaudine
Bernard
B
Lambermont
Patrizio
P
Lancellotti
Véronique
V
Roelants
Stéphan
S
Walrand
Jean-Louis
JL
Vanoverschelde
Luc
L
Pierard
André
A
Gothot
Yves
Y
Beguin
D000818:Animals; D003114:Colony-Forming Units Assay; D003326:Coronary Circulation / Q000187:drug effects*; D042783:Endothelial Cells / Q000166:cytology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006321:Heart / Q000502:physiology*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D011994:Recombinant Proteins; D013234:Stem Cells / Q000502:physiology*
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor