G-CSF treatment after myocardial infarction: impact on bone marrow-derived vs cardiac progenitor cells
Stefan Brunner1, Bruno C Huber, Rebekka Fischer
1Ludwig-Maximilians-University, Klinikum Grosshadern, Medical Department I, Munich, Germany.
Insights
Granulocyte colony-stimulating factor (G-CSF) treatment after myocardial infarction (MI) reduced bone marrow-derived progenitor cell (BMPC) migration but increased resident cardiac cells. Further research may combine G-CSF with other agents for improved cardiac repair.
Area of Science:
- Cardiovascular Research
- Stem Cell Biology
- Regenerative Medicine
Background:
- Granulocyte colony-stimulating factor (G-CSF) has known roles in stem cell transplantation and protective effects post-myocardial infarction (MI).
- G-CSF promotes bone marrow-derived progenitor cell (BMPC) mobilization and activates signaling pathways.
- The specific impact of G-CSF on BMPC migration and resident cardiac cells post-MI requires further elucidation.
Purpose of the Study:
- To investigate the effect of G-CSF on the migration of bone marrow-derived progenitor cells (BMCs) to the ischemic heart.
- To assess the impact of G-CSF on resident cardiac cells following myocardial infarction (MI).
Main Methods:
- Mice underwent bone marrow transplantation from GFP-transgenic donors and subsequent coronary artery ligation to induce MI.
- G-CSF was administered daily for six days post-MI.
- Cell populations in blood, bone marrow, and heart were analyzed by flow cytometry; growth factor expression was quantified via qRT-PCR; and cardiac perfusion was assessed using SPECT imaging.
Main Results:
- G-CSF treatment led to reduced migration of c-kit(+) and CXCR-4(+) BMCs into the ischemic myocardium.
- Expression of stem cell factor and stromal-derived factor-1 alpha was decreased in G-CSF-treated animals.
- A significant increase in resident cardiac Sca-1(+) cells was observed, but infarct size did not differ between groups.
Conclusions:
- G-CSF administration post-MI impairs BMPC migration to ischemic tissue while enhancing resident cardiac cells.
- The findings suggest that G-CSF alone may not be sufficient for optimal homing capacity.
- Combination therapy with G-CSF and other agents could potentially optimize cytokine therapy for myocardial infarction recovery.
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.
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