Therapeutic effect of fucoidan‐stimulated endothelial colony‐forming cells in peripheral ischemia |
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Authors: | G. SARLON F. ZEMANI L. DAVID J.‐P. DUONG VAN HUYEN B. DIZIER F. GRELAC S. COLLIEC‐JOUAULT I. GALY‐FAUROUX P. BRUNEVAL A.‐M. FISCHER J. EMMERICH C. BOISSON‐VIDAL |
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Affiliation: | 1. INSERM UMRS608, Marseille;2. Department of Vascular Medicine and Surgery, H?pital La Timone, AP‐HM, Marseille, France;3. Department of Molecular Genetics, Université Mohamed Boudiaf, Oran, Algeria;4. Therapol, Paris;5. Department of Pathology, H?pital Européen Georges Pompidou, AP‐HP, Paris;6. INSERM UMRS765, Paris;7. Université Paris Descartes, Sorbonne Paris Cité;8. IFREMER, Nantes;9. Department of Haematology, H?pital Européen Georges Pompidou, AP‐HP, Paris;10. Department of Vascular Medicine, H?pital Européen Georges Pompidou, AP‐HP, Paris, France |
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Abstract: | Summary. Background: Fucoidan, an antithrombotic polysaccharide, can induce endothelial colony‐forming cells (ECFC) to adopt an angiogenic phenotype in vitro. Objectives: 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. |
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Keywords: | angiogenesis endothelial colony‐forming cells fucoidan ischemia revascularization |
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