Low-molecular-weight fucoidan enhances the proangiogenic phenotype of endothelial progenitor cells

Abstract

Endothelial progenitor cell (EPC) transplantation is a potential means of inducing neovascularization in vivo. However, the number of circulating EPC is relatively small, it may thus be necessary to enhance their proangiogenic properties ex vivo prior to injection in vivo. Fucoidan has previously been shown to potentiate in vitro tube formation by mature endothelial cells in the presence of basic fibroblast growth factor (FGF-2). We therefore examined whether fucoidan, alone or combined with FGF-2, could increase EPC proangiogenic potency in vitro. EPC exposure to 10 microg/ml fucoidan induced a proangiogenic phenotype, including cell proliferation (p < 0.01) and migration (p < 0.01); moreover, differentiation into vascular cords occurred in the presence of FGF-2 (p < 0.01). This latter effect correlated with upregulation of the cell-surface #alpha6 integrin subunit of the laminin receptor (p < 0.05). Compared to untreated HUVEC, untreated EPC #alpha6 expression and adhesion to laminin were enhanced two-fold. Fucoidan treatment further enhanced HUVEC but not EPC adhesion to laminin. These results show that fucoidan enhances the proangiogenic properties of EPC and suggest that ex vivo fucoidan preconditioning of EPC might lead to increased neovascularization when injected into ischemic tissues.

α6-Integrin Subunit Plays a Major Role in the Proangiogenic Properties of Endothelial Progenitor Cells

“…11 ECFC surface expression of ␣6 is upregulated by growth factors, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 12 ; this correlates with enhanced formation of vascular tubes in vitro. 13 To our knowledge, the role of ␣6 expression by ECFCs in adult vasculogenesis has not been investigated. Therefore, we examined the influence of ␣6 expression on the proangiogenic properties of ECFCs and especially on its possible involvement in ECFC recruitment to sites of ischemia.…”

Advances in Regenerative Medicine

“…Fucoidan, a high molecular weight sulphated polysaccharide, also favourably enhanced the migratory potential of pre-treated EPCs in vitro. Although alone it did not promote angiogenesis, treatment with fucoidan potentiated the angiogenenic effect of bFGF in EPCs (Zemani et al, 2005). Du et al preconditioned skeletal myoblasts with lithium chloride and showed enhanced cell survival and increased gap-junctional coupling with co-cultured neonatal cardiomyocytes, a result of increased Cx43 expression (Du et al, 2009).…”

Cytoprotection and Preconditioning for Stem Cell Therapy

“…Fucoidan, a high molecular weight sulphated polysaccharide, also favourably enhanced the migratory potential of pre-treated EPCs in vitro. Although alone it did not promote angiogenesis, treatment with fucoidan potentiated the angiogenenic effect of bFGF in EPCs (Zemani et al, 2005). Du et al preconditioned skeletal myoblasts with lithium chloride and showed enhanced cell survival and increased gap-junctional coupling with co-cultured neonatal cardiomyocytes, a result of increased Cx43 expression (Du et al, 2009).…”