title: Flt3 ligand synergizes with granulocyte-colony-stimulating factor in bone marrow mobilization to improve functional outcome after spinal cord injury in the rat.
abstract: OBJECTIVE
  The effect of granulocyte-colony-stimulating factor (G-CSF) and/or the cytokine fms-like thyrosin kinase 3 (Flt3) ligand on functional outcome and tissue regeneration was studied in a rat model of spinal cord injury (SCI).
  
  
  METHODS
  Rats with a balloon-induced compression lesion were injected with G-CSF and/or Flt3 ligand to mobilize bone marrow cells. Behavioral tests (Basso-Beattie-Bresnahan and plantar test), blood counts, morphometric evaluation of the white and gray matter, and histology were performed 5 weeks after SCI.
  
  
  RESULTS
  The mobilization of bone marrow cells by G-CSF, Flt3 ligand and their combination improved the motor and sensory performance of rats with SCI, reduced glial scarring, increased axonal sprouting and spared white and gray matter in the lesion. The best results were obtained with a combination of G-CSF and Flt3. G-CSF alone or in combination with Flt3 ligand significantly increased the number of white blood cells, but not red blood cells or hemoglobin content, during and after the time-course of bone marrow stimulation. The combination of factors led to infiltration of the lesion by CD11b(+) cells.
  
  
  CONCLUSIONS
  The observed improvement in behavioral and morphologic parameters and tissue regeneration in animals with SCI treated with a combination of both factors could be associated with a prolonged time-course of mobilization of bone marrow cells. The intravenous administration of G-CSF and/or Flt3 ligand represents a safe and effective treatment modality for SCI.
authors.affiliation: Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Lucia
authors.initials: L
authors.lastname: Urdziková
authors.forename: Katarína
authors.initials: K
authors.lastname: Likavčanová-Mašínová
authors.forename: Václav
authors.initials: V
authors.lastname: Vaněček
authors.forename: Jiří
authors.initials: J
authors.lastname: Růžička
authors.forename: Jiří
authors.initials: J
authors.lastname: Sedý
authors.forename: Eva
authors.initials: E
authors.lastname: Syková
authors.forename: Pavla
authors.initials: P
authors.lastname: Jendelová
mesh_terms: D000818:Animals; D001519:Behavior / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D048091:Guided Tissue Regeneration; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012677:Sensation / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology / Q000601:surgery / Q000628:therapy*
chemical_list: D008565:Membrane Proteins; C084881:flt3 ligand protein; D016179:Granulocyte Colony-Stimulating Factor