1These authors contributed equally to this study.
Therapeutic effect of fucoidan-stimulated endothelial colony-forming cells in peripheral ischemia
Article first published online: 4 JAN 2012
© 2011 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 10, Issue 1, pages 38–48, January 2012
How to Cite
SARLON, G., ZEMANI, F., DAVID, L., DUONG VAN HUYEN, J.-P., DIZIER, B., GRELAC, F., COLLIEC-JOUAULT, S., GALY-FAUROUX, I., BRUNEVAL, P., FISCHER, A.-M., EMMERICH, J. and BOISSON-VIDAL, C. (2012), Therapeutic effect of fucoidan-stimulated endothelial colony-forming cells in peripheral ischemia. Journal of Thrombosis and Haemostasis, 10: 38–48. doi: 10.1111/j.1538-7836.2011.04554.x
- Issue published online: 4 JAN 2012
- Article first published online: 4 JAN 2012
- Accepted manuscript online: 8 NOV 2011 10:02AM EST
- Received 5 March 2011, accepted 27 October 2011
- endothelial colony-forming cells;
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.