title: Combinatorial G-CSF/AMD3100 treatment in cardiac repair after myocardial infarction.
abstract: OBJECTIVE
  Several studies suggest that circulating bone marrow derived stem cells promote the regeneration of ischemic tissues. For hematopoietic stem cell transplantation combinatorial granulocyte-colony stimulating factor (G-CSF)/Plerixafor (AMD3100) administration was shown to enhance mobilization of bone marrow derived stem cells compared to G-CSF monotherapy. Here we tested the hypothesis whether combinatorial G-CSF/AMD3100 therapy has beneficial effects in cardiac recovery in a mouse model of myocardial infarction.
  
  
  METHODS
  We analyzed the effect of single G-CSF (250 µg/kg/day) and combinatorial G-CSF/AMD3100 (100 µg/kg/day) treatment on cardiac morphology, vascularization, and hemodynamics 28 days after permanent ligation of the left anterior descending artery (LAD). G-CSF treatment started directly after induction of myocardial infarction (MI) for 3 consecutive days followed by a single AMD3100 application on day three after MI in the G-CSF/AMD3100 group. Cell mobilization was assessed by flow cytometry of blood samples drawn from tail vein on day 0, 7, and 14.
  
  
  RESULTS
  Peripheral blood analysis 7 days after MI showed enhanced mobilization of white blood cells (WBC) and endothelial progenitor cells (EPC) upon G-CSF and combinatorial G-CSF/AMD3100 treatment. However, single or combinatorial treatment showed no improvement in survival, left ventricular function, and infarction size compared to the saline treated control group 28 days after MI. Furthermore, no differences in histology and vascularization of infarcted hearts could be observed.
  
  
  CONCLUSIONS
  Although the implemented treatment regimen caused no adverse effects, our data show that combinatorial G-CSF/AMD therapy does not promote myocardial regeneration after permanent LAD occlusion.
authors.affiliation: Berlin Brandenburg Center for Regenerative Therapies (BCRT), Berlin, Germany; Department of Cardiology, Campus Virchow Klinikum, Charité Berlin, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: Rüder
authors.affiliation: Berlin Brandenburg Center for Regenerative Therapies (BCRT), Berlin, Germany; Department of Cardiology, Campus Virchow Klinikum, Charité Berlin, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Haase
authors.affiliation: Berlin Brandenburg Center for Regenerative Therapies (BCRT), Berlin, Germany.
authors.forename: Annalena
authors.initials: A
authors.lastname: Krost
authors.affiliation: Berlin Brandenburg Center for Regenerative Therapies (BCRT), Berlin, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Langwieser
authors.affiliation: Berlin Brandenburg Center for Regenerative Therapies (BCRT), Berlin, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Peter
authors.affiliation: Berlin Brandenburg Center for Regenerative Therapies (BCRT), Berlin, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kamann
authors.affiliation: Berlin Brandenburg Center for Regenerative Therapies (BCRT), Berlin, Germany; Department of Cardiology, Campus Virchow Klinikum, Charité Berlin, Germany.
authors.forename: Dietlind
authors.initials: D
authors.lastname: Zohlnhöfer
mesh_terms: D000818:Animals; D001596:Benzylamines; D000080027:Cyclams; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006321:Heart / Q000503:physiopathology*; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor