Influence of Fucoidan Extracts from Different Fucus Species on Adult Stem Cells and Molecular Mediators in In Vitro Models for Bone Formation and Vascularization

Abstract

Fucoidans, sulfated polysaccharides extracted from brown algae, are marine products with the potential to modulate bone formation and vascularization processes. The bioactivity and safety of fucoidans are highly associated with their chemical structure, which may vary with algae species and extraction method. Thus, in depth evaluation of fucoidan extracts in terms of endotoxin content, cytotoxicity, and their detailed molecular biological impact on the individual cell types in bone is needed. In this study, we characterized fucoidan extracts from three different Fucus species including Fucus vesiculosus (Fv), Fucus serratus (Fs), and Fucus distichus subsp. evanescens (Fe) for their chemical features, endotoxin content, cytotoxicity, and bioactive effects on human outgrowth endothelial cells (OEC) and human mesenchymal stem cells (MSC) as in vitro models for bone function and vascularization. Extracts contained mainly high molecular weight (HMW) fucoidans and were free of endotoxins that may cause inflammation or influence vascularization. OEC tolerated fucoidan concentrations up to 200 µg/mL, and no indication of cytotoxicity was observed. The inflammatory response, however, investigated by real-time PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) and endothelial barrier assessed by impedance measurement differed for the individual extracts. MSC in comparison with endothelial cells were more sensitive to fucoidans and showed partly reduced metabolic activity and proliferation at higher doses of fucoidans. Further results for MSC indicated impaired osteogenic functions in alkaline phosphatase and calcification assays. All tested extracts consistently lowered important molecular mediators involved in angiogenesis, such a VEGF (vascular endothelial growth factor), ANG-1 (angiopoietin 1), and ANG-2 (angiopoietin 2), as indicated by RT-PCR and ELISA. This was associated with antiangiogenic effects at the functional level using selected extracts in co-culture models to mimic bone vascularization processes during bone regeneration or osteosarcoma.

Application of fucoidan as treatment for cardiovascular and cerebrovascular diseases

“…Mice induced with chronic hypoxia for 35 days were given fucoidan P-selectin antibody, which significantly improved blood vessel remodeling and restored right ventricular function. 107 Fucoidan extract with high fucose and sulfate contents had an inhibitory effect in an in vitro model of angiogenesis, 108 and LMWF can promote the angiogenesis- and migration-promoting activity of human endothelial cells that is induced by FGF-2, which may be conducive to blood remodeling in the ischemic area. 109 Compared with FGF-2 alone, fucoidan and FGF-2 have a greater effect on tube formation and cell migration.…”

Evaluation of the Effects of Fucoidans from Fucus Species and Laminaria hyperborea against Oxidative Stress and Iron-Dependent Cell Death

“…However, microwave irradiation and exposure to acids degrade endotoxins [57,58]. In addition, FVs had been previously shown to be ultra-pure with respect to endotoxins (below 100 EU/mL) [59]. In general, we considered all extracts to be endotoxin-free.…”

Efficacy of marine bioactive compound fucoidan for bone regeneration and implant fixation in sheep

“…22 A microwave-assisted method was used at the SDU 23 to extract FUC from Fucus serratus. 24 Different extraction methods and molecular weight were used to see if it had an impact on bone regeneration and implant fixation.…”