Abstract
The marine origin polysaccharide fucoidan combines multiple biological activities. As demonstrated by various studies in vitro and in vivo, fucoidans show anti-viral, anti-tumor, anti-oxidant, anti-inflammatory and anti-coagulant properties, although the detailed molecular action remains to be elucidated. The aim of the present study is to assess the impact of crude fucoidan extracts, on the formation of vascular structures in co-culture models relevant for bone vascularization during bone repair and for vascularization processes in osteosarcoma. The co-cultures consisted of bone marrow derived mesenchymal stem cells, respectively the osteosarcoma cell line MG63, and human blood derived outgrowth endothelial cells (OEC). The concentration dependent effects on the metabolic activity on endothelial cells and osteoblast cells were first assessed using monocultures of OEC, MSC and MG63 suggesting a concentration of 100 µg/mL as a suitable concentration for further experiments. In co-cultures fucoidan significantly reduced angiogenesis in MSC/OEC but also in MG63/OEC co-cultures suggesting a potential application of fucoidan to lower the vascularization in bone tumors such as osteosarcoma. This was associated with a decrease in VEGF (vascular endothelial growth factor) and SDF-1 (stromal derived factor-1) on the protein level, both related to the control of angiogenesis and furthermore discussed as crucial factors in osteosarcoma progression and metastasis. In terms of bone formation, fucoidan slightly lowered on the calcification process in MSC monocultures and MSC/OEC co-cultures. In summary, these data suggest the suitability of lower fucoidan doses to limit angiogenesis for instance in osteosarcoma.
Highlights
Vascularization, the formation of blood vessels, plays an essential role in bone repair [1,2,3] and normal bone physiology as well as in bone tumor development [4]
The MTS assays were performed to examine a potential effect of fucoidan on the metabolic activities of mesenchymal stem cells (MSCs), MG63 and outgrowth endothelial cells (OEC) in monocultures at day 10 (Figure 1) using different concentrations of fucoidan
For 100 μg/mL (Figure 1), the metabolic activity of MSC and OECs showed only a slight but no significant reduction in fucoidan treated group compared to controls
Summary
Vascularization, the formation of blood vessels, plays an essential role in bone repair [1,2,3] and normal bone physiology as well as in bone tumor development [4]. A series of studies imply the contribution of stem cells and progenitor cells such as circulating endothelial progenitor cells in the formation of new blood vessels [5,6]. In bone tumors such as osteosarcomas angiogenesis plays a key role mediating tumor growth and formation of metastasis [7]. Molecular mechanisms guiding tumor-induced angiogenesis and neovascularization during bone regeneration seem to be at least similar [8]. Co-culture systems have been shown to serve as highly relevant in vitro
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