Alginate oligosaccharides stimulate VEGF-mediated growth and migration of human endothelial cells

Abstract

Alginate oligosaccharides cleaved from alginic acid polysaccharides of seaweed were tested to determine their ability to enhance proliferation and migration of human umbilical vein endothelial cells. A mixture of alginate oligosaccharides (5 microg/ml in culture broth) stimulated endothelial cell growth, [(3)H]thymidine uptake and migration in the presence of recombinant vascular endothelial growth factor 165 (VEGF(165)). In contrast, a high concentration mixture of the oligosaccharides ( approximately 100 microg/ml) suppressed cell growth. The stimulatory activity was comparable to that of heparin, with affinity to VEGF(165), and decreased on heparin-induced stimulation. Each effective oligosaccharide had guluronic acid at the reducing end. A mixture of alginate oligosaccharides (5 microg/ml) and the most paragraph signeffective fraction (1 microg/ml) stimulated endothelial cell migration. In the presence of VEGF and heparin, some alginate oligosaccharides with the peripheral guluronic acid demonstrated marked stimulatory effects, and one fraction also showed a migratory effect. These findings indicate novel activities of alginate oligosaccharide(s) in endothelial cell growth and migration and suggest synergistic and/or stabilizing effects on VEGF(165)-dependent stimulation of endothelial cells.

Effects of sulfated fucan, ascophyllan, from the brown Alga Ascophyllum nodosum on various cell lines: A comparative study on ascophyllan and fucoidan

“…To our knowledge, this is the first report that ascophyllan or even algal-derived sulfated polysaccharides can promote the growth of certain cell lines under normal growth conditions. Regarding the effects of saccharides on the growth of certain mammalian cells, it has been reported that alginate oligosaccharides stimulate or enhance vascular endothelial growth factor-mediated growth of human endothelial cells and the growth of keratinocyte in the presence of epidermal growth factor (32,33). Since no significant effects of alginate oligosaccharides were observed on the cells in the absence of the growth factors, it has been considered that alginate oligosaccharides may stimulate proliferative activity of growth factors by a synergistic mechanism.…”

Plant Cell Wall Degradation by Saprophytic Bacillus subtilis Strains: Gene Clusters Responsible for Rhamnogalacturonan Depolymerization

“…Strain 168 RG lyases, especially YesX, release the unsaturated RG disaccharide from substrates. Oligosaccharides called oligosaccharins show physiological functions such as a bifidus factor, an elicitor of plant growth, a growth enhancer of human endothelial cells and keratinocytes, and an inducer of cytokine production from mouse macrophage cells (1,5,18,19,21,22,27). The unsaturated RG disaccharide "lepidimoide" has been isolated from seeds of cress (Lepidium sativum L.) and shown to function as an allelopathic factor for plants (12,53).…”

Swelling and Mechanical Properties of Alginate Hydrogels with Respect to Promotion of Neural Growth

“…56,57 Most recently, wobble oligosaccharide motifs of chondroitin sulfate/dermatan sulfate proteoglycans had been demonstrated to induce signaling pathways that are essential for the proliferation, self-renewal, and cell lineage commitment of neural stem cells. 58 Although stiff alginate hydrogels were described as an inert matrix, alginate-derived oligosaccharides have been reported to costimulate growth factormediated proliferation, migration, and adhesion of endothelial cells, keratinocytes, and skin fibroblasts in vitro; [59][60][61] cytokine production by RAW264.7 cells; 62 and phagocytic activity of peritoneal monocytes. 63 The density of substrateimmobilized signaling molecules is crucial to initiate extracellular signaling events that lead to cell differentiation, adhesion, growth, and migration, and this must be considered during scaffold designing.…”