Effects of granulocyte-colony-stimulating factor on progenitor cell mobilization and heart perfusion and function in
Marie Delgaudine1, Bernard Lambermont, Patrizio Lancellotti
1Giga-Research, Hematology Unit, University of Liège, Liège, Belgium.
Insights
Granulocyte-colony-stimulating factor (G-CSF) mobilizes hematopoietic (HPC) and endothelial progenitor cells (EPC) into peripheral blood. G-CSF impacts normal heart function, enhancing perfusion but impairing hemodynamics.
Area of Science:
- Stem cell biology
- Cardiovascular research
- Hematology
Background:
- Granulocyte-colony-stimulating factor (G-CSF) is investigated for stem cell mobilization in cardiac regeneration.
- Mobilization of hematopoietic (HPC), mesenchymal (MPC), and endothelial progenitor cells (EPC) requires optimization.
- The effect of G-CSF on normal heart perfusion and function is largely unstudied.
Purpose of the Study:
- To investigate the mobilization patterns of HPC, MPC, and EPC in response to G-CSF.
- To evaluate the impact of G-CSF on myocardial perfusion and cardiac function in normal mice.
Main Methods:
- Normal mice received daily G-CSF injections for 1-10 days.
- Peripheral blood and bone marrow were analyzed for progenitor cells using flow cytometry and colony assays.
- Cardiac function and perfusion were assessed via echocardiography, microSPECT imaging, and cardiac catheterization.
Main Results:
- G-CSF induced distinct mobilization patterns for HPC, EPC, and CFU-F progenitors in peripheral blood.
- Bone marrow showed increased EPC production but decreased CFU-F formation post-G-CSF treatment.
- G-CSF improved myocardial perfusion and vascularization but led to impaired cardiac hemodynamics.
Conclusions:
- G-CSF differentially mobilizes progenitor cells into peripheral blood.
- G-CSF significantly affects both the perfusion and functional hemodynamics of a normal heart.
Background Aims:
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.
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