Wang Fanlu, Schmidt Harald, Pavleska Dijana, Wermann Thees, Seekamp Andreas, Fuchs Sabine
Experimental Trauma Surgery, University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
MetaPhysiol, Am Römerberg, 55270 Essenheim, Germany.
Mar Drugs. 2017 Jun 20;15(6):186. doi: 10.3390/md15060186.
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.
海洋来源的多糖岩藻聚糖具有多种生物活性。体外和体内的各种研究表明，岩藻聚糖具有抗病毒、抗肿瘤、抗氧化、抗炎和抗凝血特性，尽管其详细的分子作用仍有待阐明。本研究的目的是评估粗制岩藻聚糖提取物对与骨修复过程中骨血管化以及骨肉瘤血管化过程相关的共培养模型中血管结构形成的影响。共培养由骨髓来源的间充质干细胞、骨肉瘤细胞系MG63以及人血来源的内皮祖细胞（OEC）组成。首先使用OEC、MSC和MG63的单培养评估了岩藻聚糖对内皮细胞和成骨细胞代谢活性的浓度依赖性影响，结果表明100μg/mL的浓度适合进一步实验。在共培养中，岩藻聚糖显著降低了MSC/OEC以及MG63/OEC共培养中的血管生成，这表明岩藻聚糖在降低骨肉瘤等骨肿瘤血管化方面具有潜在应用价值。这与蛋白水平上血管内皮生长因子（VEGF）和基质细胞衍生因子-1（SDF-1）的减少有关，这两种因子都与血管生成的控制有关，并且在骨肉瘤进展和转移中被进一步讨论为关键因素。在骨形成方面，岩藻聚糖在MSC单培养和MSC/OEC共培养中略微降低了钙化过程。总之，这些数据表明较低剂量的岩藻聚糖适合用于限制血管生成，例如在骨肉瘤中。
