Spontaneous and granulocyte&#x2013;colony-stimulating factor-enhanced marrow response and progenitor cell mobilization in mice after myocardial infarction.
OBJECTIVE
Hematopoietic (HPC), mesenchymal (MPC) and/or endothelial (EPC) progenitor cells are being studied to repair the myocardium after acute or chronic ischemia. We examined marrow response to myocardial infarction (MI) and the ability of granulocyte–colony-stimulating factor (G-CSF) to enhance mobilization of HPC, MPC and EPC in peripheral blood (PB) and bone marrow (BM) of MI mice.


METHODS
We induced MI in C57Bl/6 mice, while sham-operated (SO) animals were similarly operated on but without coronary artery ligation. Animals were treated with either saline or G-CSF, from day −5 to day +5 after MI or from day 0 to day +5. Progenitor cell numbers in PB and BM were evaluated by fluorescence-activated cell sorting (FACS) analysis and cell culture.


RESULTS
White blood cells (WBC) decreased in BM and increased in PB after MI; G-CSF amplified this effect in BM but not in PB. HPC numbers decreased in BM after MI, while HPC and granulocyte–macrophage colony-forming units (GM-CFU) increased in PB only after G-CSF treatment, and more prominently so in MI than in SO mice. MPC and fibroblast–colony-forming units (F-CFU) as well as EPC were mobilized into the PB after MI and further after G-CSF treatment. Plasma troponin T concentrations decreased after G-CSF treatment.


CONCLUSIONS
BM is globally affected by acute MI, but not simple body injury, with intense mobilization of marrow MPC and EPC into the PB but inhibition of HPC. Progenitor cell entry into the PB may be paralleled by depletion of their BM pools. G-CSF is required for HPC mobilization and enhances MPC and EPC entry into the PB.
Giga-Research, Hematology Unit, University of Li&#x00E8;ge, Li&#x00E8;ge, Belgium.
Marie
M
Delgaudine
André
A
Gothot
Yves
Y
Beguin
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D003114:Colony-Forming Units Assay; D042783:Endothelial Cells / Q000473:pathology; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects; D019650:Hematopoietic Stem Cell Mobilization; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D016179:Granulocyte Colony-Stimulating Factor