title: Modification of post-myocardial infarction granulocyte-colony stimulating factor therapy with myelo-suppressives.
abstract: BACKGROUND
  The purpose of the present study was to investigate the effect of granulocyte colony-stimulating factor (G-CSF) in combination with myelo-suppressives on post-myocardial infarction (MI) myocardial repair.
  
  
  RESULTS
  Twenty-four hours after 30-min ischemia and reperfusion (day 0), rabbits were assigned to 4 treatment groups: myelo-suppressives (M group), G-CSF (G group), the 2 in combination (MG group) or saline (S group). Significantly greater numbers of circulating stem cells were seen in the MG group than in the G group, with attenuated leukocytosis. In addition, MG caused the greatest upregulation of stromal cell-derived factor (SDF)-1 within the infarcted myocardium and thus recruitment of stem cells from the circulation into the infarcted tissue. This led to enhanced myocardial repair, as indicated by the numbers of bone marrow cell-derived cardiomyocytes and endothelial cells, reduction in scar tissue, improvement in cardiac function and reduction in left ventricular remodeling during the chronic phase of MI. These beneficial effects were entirely abolished by the administration of a CXCR4 antagonist AMD3100, which indicates the importance of CXCR4/SDF-1-axis as a mechanism underlying myocardial repair.
  
  
  CONCLUSIONS
  The combination of G-CSF and myelo-suppressives may be a useful new therapy that overcomes the insufficiency seen with G-CSF alone.
authors: Department of Cardiology, Regeneration Medicine and Bioethics, Gifu University Graduate School of Medicine.
authors: Yu
authors: Y
authors: Misao
authors: Masazumi
authors: M
authors: Arai
authors: Takamasa
authors: T
authors: Ohno
authors: Hiroaki
authors: H
authors: Ushikoshi
authors: Hirohito
authors: H
authors: Onogi
authors: Hiroyuki
authors: H
authors: Kobayashi
authors: Genzou
authors: G
authors: Takemura
authors: Shinya
authors: S
authors: Minatoguchi
authors: Takako
authors: T
authors: Fujiwara
authors: Hisayoshi
authors: H
authors: Fujiwara
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001596:Benzylamines; D001772:Blood Cell Count; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology; D000080027:Cyclams; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004452:Echocardiography; D042783:Endothelial Cells / Q000473:pathology; D005472:Fluorouracil / Q000627:therapeutic use*; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology; D011817:Rabbits; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000502:physiology; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D001596:Benzylamines; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D000080027:Cyclams; D006571:Heterocyclic Compounds; D007166:Immunosuppressive Agents; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; C088327:plerixafor; D005472:Fluorouracil