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G-CSF displays restricted ability to promote Sca-1(+) cardiac stem cell proliferation in vitro
Haijian Luo1, Giulio Bassi, Maddalena Tessari
1Interdepartmental Centre LURM, University of Verona, 37134, Verona, Italy, haijian.luo@manchester.ac.uk.
Insights
Granulocyte colony-stimulating factor (G-CSF) receptor is present on cardiac stem cells (CSCs). G-CSF treatment moderately stimulates CSC proliferation, offering insights for heart disease therapies.
Area of Science:
- Cardiovascular Research
- Stem Cell Biology
- Regenerative Medicine
Background:
- Granulocyte colony-stimulating factor (G-CSF) is investigated for cardiac cell therapy, with myocardial homing of bone marrow cells implicated in repair.
- Activating resident cardiac stem cells (CSCs) for proliferation remains a challenge in G-CSF therapy.
Purpose of the Study:
- To determine if G-CSF receptors are expressed on adult resident Sca-1(+) CSCs.
- To evaluate the impact of G-CSF on CSC proliferation.
Main Methods:
- Isolation of highly purified Sca-1(+) CSCs from adult male C57BL/6 mice using magnetic-activated cell sorting.
- Detection of G-CSF receptor expression via immunofluorescence staining and Western blotting.
- Assessment of G-CSF's effect on CSC proliferation in vitro.
Main Results:
- G-CSF receptor expression was confirmed on adult resident Sca-1(+) CSCs.
- G-CSF exposure induced a time-dependent, self-limiting acceleration of the cell cycle.
- CSC proliferation showed a restricted response to G-CSF treatment.
Conclusions:
- The findings provide novel insights into the interaction between cardiac G-CSF therapy and resident stem cell activation.
- Further research into CSC-G-CSF mechanisms may enable synergistic therapeutic strategies for heart disease.
Abstract:
Granulocyte colony-stimulating factor (G-CSF) is a controversial chemical in cardiac cell therapy. Myocardial homing of mobilized bone marrow-derived cells is thought to play a critical role in observed G-CSF-induced cardiac repair; meanwhile, the activation of proliferative potential of cardiac stem cells (CSCs) residing in the heart is a significant challenge. The present study aims to investigate whether G-CSF receptor is expressed in adult resident Sca-1(+) CSCs and determine the effect of G-CSF treatment on the proliferation of CSCs. For cardiac cells isolation, 12-week-old male C57BL/6 mice were anesthetized in a chamber containing 2.5% isoflurane in oxygen, euthanized by CO2 inhalation and then sacrificed by cervical dislocation. Magnetic-activated cell sorting was employed to acquire highly purified Sca-1(+) CSCs. We found that G-CSF receptor was expressed in adult resident Sca-1(+) CSCs by immunofluorescence staining and Western blotting. Exposure of Sca-1(+) cells to G-CSF in the culture medium for 72 h induced time-dependent but self-limiting cell cycle acceleration with a restricted effect on the CSC proliferation. As a result, it has provided a new insight to focus on the association between cardiac G-CSF therapy and adult resident stem cell activation. It may suggest gaining a deeper insight into the mechanisms of the interaction between CSCs and G-CSF to develop a synergistic strategy based on resident stem cell and G-CSF therapy for heart disease.
