Abstract
Background: Human milk feedings are thought to reduce certain health risks such as the development of retinopathy due to hyperoxia and neovasularization in the neonatal period. As a new approach for the prevention and therapy of diseases involving the formation of new blood vessels, synthetic oligosaccharide ligands for cell adhesion molecules revealed anti-angiogenic effects in vitro. Human milk, however, is a natural reservoir of oligosaccharides structurally resembling selectin ligands such as the tetrasaccharide sialyl-Lewis x. Here, we assessed the properties of human milk oligosaccharides to modulate angiogenesis in vitro and in vivo.
Methods: In vitro tube formation assays were performed using bovine retinal endothelial cells (BREC) on collagen-coated dextrane beads in fibrin gels containing isolated neutral (nHMO) or sialylated human milk oligosaccharides (sHMO) at concentrations of 10, 25, and 100ìg/mL. After 48h incubation tubular structures radiating from the beads' surface and protruding into the gel were counted. To confirm the anti-angiogenic capacity of HMO in vivo, Matrigel™ plugs (containing heparin, VEGF and bFGF) supplemented with 100ìg/mL of nHMO or sHMO were subcutaneously injected in mice. The gel plugs were recovered five days after implantation and inspected for the formation of blood filled microvessels.
Results: In contrast to nHMO, sHMO showed anti-antigenic potency in a concentration dependent manner with a maximum effect of about 40% at 25ìg/mL. The differences of the effects of nHMO and sHMO were significant at 25ìg/mL (p<0.005) and 100ìg/mL (p <0.05). While the nHMO containing plug showed high cellularity and was partially congested with blood, the plug spiked with sHMO was transparent indicating the inhibition of neovascularization.
Conclusion: Human milk oligosaccharides containing sialic acid revealed anti-angiogenic properties in vitro and in vivo. These potentially beneficial effects may explain why diseases associated with angiogenesis such as retinopathy were reported to be less prevalent in breastfed infants.
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Rudloff, S., Schneider, D., Kunz, C. et al. 230 Human Milk as a Natural Source of Anti-Angiogenic Compounds. Pediatr Res 56, 503 (2004). https://doi.org/10.1203/00006450-200409000-00253
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DOI: https://doi.org/10.1203/00006450-200409000-00253