title: G-CSF displays restricted ability to promote Sca-1(+) cardiac stem cell proliferation in vitro.
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.
authors.affiliation: Interdepartmental Centre LURM, University of Verona, 37134, Verona, Italy, haijian.luo@manchester.ac.uk.
authors.forename: Haijian
authors.initials: H
authors.lastname: Luo
authors.forename: Giulio
authors.initials: G
authors.lastname: Bassi
authors.forename: Maddalena
authors.initials: M
authors.lastname: Tessari
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yang
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Faggian
mesh_terms: D053687:Adult Stem Cells / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000950:Antigens, Ly; D002453:Cell Cycle / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D016179:Granulocyte Colony-Stimulating Factor