title: Therapeutic effect of fucoidan-stimulated endothelial  colony-forming cells in peripheral ischemia.
abstract: BACKGROUND
  Fucoidan, an antithrombotic polysaccharide, can induce endothelial colony-forming cells (ECFC) to adopt an angiogenic phenotype in vitro.
  
  
  OBJECTIVE
  We evaluated the effect of fucoidan on vasculogenesis induced by ECFC in vivo.
  
  
  METHODS
  We used a murine hindlimb ischemia model to probe the synergic role of fucoidan-treatment and ECFC infusion during tissue repair.
  
  
  RESULTS
  We found that exposure of ECFC to fucoidan prior to their intravenous injection improved residual muscle blood flow and increased collateral vessel formation. Necrosis of ischemic tissue was significantly reduced on day 14, to 12.1% of the gastronecmius cross-sectional surface area compared with 40.1% in animals injected with untreated-ECFC. ECFC stimulation with fucoidan caused a rapid increase in cell adhesion to activated endothelium in flow conditions, and enhanced transendothelial extravasation. Fucoidan-stimulated ECFC were resistant to shear stresses of up to 21 dyn cm(-2). Direct binding assays showed strong interaction of fucoidan with displaceable binding sites on the ECFC membrane. Bolus intramuscular administration of fucoidan 1 day after surgery reduces rhabdomyolysis. Mice injected with fucoidan (15 mg kg(-1)) had significantly lower mean serum creatine phosphokinase (CPK) activity than control animals. This CPK reduction was correlated with muscle preservation against necrosis (P < 0.001).
  
  
  CONCLUSIONS
  Fucoidan greatly increases ECFC-mediated angiogenesis in vivo. Its angiogenic effect would be due in part to its transportation to the ischemic site and its release after displacement by proteoglycans present in the extracellular matrix. The use of ECFC and fucoidan together, will be an efficient angiogenesis strategy to provide therapeutic neovascularization.
authors: INSERM UMRS608, Marseille, France.
authors: G
authors: G
authors: Sarlon
authors: F
authors: F
authors: Zemani
authors: L
authors: L
authors: David
authors: J P
authors: JP
authors: Duong Van Huyen
authors: B
authors: B
authors: Dizier
authors: F
authors: F
authors: Grelac
authors: S
authors: S
authors: Colliec-Jouault
authors: I
authors: I
authors: Galy-Fauroux
authors: P
authors: P
authors: Bruneval
authors: A M
authors: AM
authors: Fischer
authors: J
authors: J
authors: Emmerich
authors: Catherine
authors: C
authors: Boisson-Vidal
mesh_terms: D000818:Animals; D000925:Anticoagulants; D042783:Endothelial Cells / Q000187:drug effects / Q000637:transplantation*; D007511:Ischemia / Q000188:drug therapy*; D051379:Mice; D009132:Muscles / Q000098:blood supply; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011134:Polysaccharides / Q000008:administration & dosage / Q000627:therapeutic use*; D012039:Regional Blood Flow / Q000187:drug effects; D033581:Stem Cell Transplantation; D013234:Stem Cells
chemical_list: D000925:Anticoagulants; D011134:Polysaccharides; C007789:fucoidan