Influence of Fucoidan Extracts from Different Fucus Species on Adult Stem Cells and Molecular Mediators in In Vitro Models for Bone Formation and Vascularization
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 extracti...
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MDPI AG
2021-03-01
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author | Fanlu Wang Yuejun Xiao Sandesh Neupane Signe Helle Ptak Ramona Römer Junyu Xiong Julia Ohmes Andreas Seekamp Xavier Fretté Susanne Alban Sabine Fuchs |
author_facet | Fanlu Wang Yuejun Xiao Sandesh Neupane Signe Helle Ptak Ramona Römer Junyu Xiong Julia Ohmes Andreas Seekamp Xavier Fretté Susanne Alban Sabine Fuchs |
author_sort | Fanlu Wang |
collection | DOAJ |
description | 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 <i>Fucus</i> species including <i>Fucus vesiculosus</i> (Fv), <i>Fucus serratus</i> (Fs), and <i>Fucus distichus</i> subsp. <i>evanescens</i> (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. |
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spelling | doaj.art-b5b1ce92e87242fb802049581ca426242023-11-21T13:17:14ZengMDPI AGMarine Drugs1660-33972021-03-0119419410.3390/md19040194Influence of Fucoidan Extracts from Different Fucus Species on Adult Stem Cells and Molecular Mediators in In Vitro Models for Bone Formation and VascularizationFanlu Wang0Yuejun Xiao1Sandesh Neupane2Signe Helle Ptak3Ramona Römer4Junyu Xiong5Julia Ohmes6Andreas Seekamp7Xavier Fretté8Susanne Alban9Sabine Fuchs10Experimental Trauma Surgery, Department of Orthopedics and Trauma Surgery, University Medical Center Schleswig-Holstein, 24105 Kiel, GermanyExperimental Trauma Surgery, Department of Orthopedics and Trauma Surgery, University Medical Center Schleswig-Holstein, 24105 Kiel, GermanyDepartment of Pharmaceutical Biology, Pharmaceutical Institute, Kiel University, 24148 Kiel, GermanySDU Chemical Engineering, University of Southern Denmark, 5230 Odense, DenmarkExperimental Trauma Surgery, Department of Orthopedics and Trauma Surgery, University Medical Center Schleswig-Holstein, 24105 Kiel, GermanyExperimental Trauma Surgery, Department of Orthopedics and Trauma Surgery, University Medical Center Schleswig-Holstein, 24105 Kiel, GermanyExperimental Trauma Surgery, Department of Orthopedics and Trauma Surgery, University Medical Center Schleswig-Holstein, 24105 Kiel, GermanyExperimental Trauma Surgery, Department of Orthopedics and Trauma Surgery, University Medical Center Schleswig-Holstein, 24105 Kiel, GermanySDU Chemical Engineering, University of Southern Denmark, 5230 Odense, DenmarkDepartment of Pharmaceutical Biology, Pharmaceutical Institute, Kiel University, 24148 Kiel, GermanyExperimental Trauma Surgery, Department of Orthopedics and Trauma Surgery, University Medical Center Schleswig-Holstein, 24105 Kiel, GermanyFucoidans, 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 <i>Fucus</i> species including <i>Fucus vesiculosus</i> (Fv), <i>Fucus serratus</i> (Fs), and <i>Fucus distichus</i> subsp. <i>evanescens</i> (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.https://www.mdpi.com/1660-3397/19/4/194fucoidanmesenchymal stem cells (MSC)outgrowth endothelial cells (OEC)angiogenesisbone vascularization |
spellingShingle | Fanlu Wang Yuejun Xiao Sandesh Neupane Signe Helle Ptak Ramona Römer Junyu Xiong Julia Ohmes Andreas Seekamp Xavier Fretté Susanne Alban Sabine Fuchs Influence of Fucoidan Extracts from Different Fucus Species on Adult Stem Cells and Molecular Mediators in In Vitro Models for Bone Formation and Vascularization Marine Drugs fucoidan mesenchymal stem cells (MSC) outgrowth endothelial cells (OEC) angiogenesis bone vascularization |
title | Influence of Fucoidan Extracts from Different Fucus Species on Adult Stem Cells and Molecular Mediators in In Vitro Models for Bone Formation and Vascularization |
title_full | Influence of Fucoidan Extracts from Different Fucus Species on Adult Stem Cells and Molecular Mediators in In Vitro Models for Bone Formation and Vascularization |
title_fullStr | Influence of Fucoidan Extracts from Different Fucus Species on Adult Stem Cells and Molecular Mediators in In Vitro Models for Bone Formation and Vascularization |
title_full_unstemmed | Influence of Fucoidan Extracts from Different Fucus Species on Adult Stem Cells and Molecular Mediators in In Vitro Models for Bone Formation and Vascularization |
title_short | Influence of Fucoidan Extracts from Different Fucus Species on Adult Stem Cells and Molecular Mediators in In Vitro Models for Bone Formation and Vascularization |
title_sort | influence of fucoidan extracts from different fucus species on adult stem cells and molecular mediators in in vitro models for bone formation and vascularization |
topic | fucoidan mesenchymal stem cells (MSC) outgrowth endothelial cells (OEC) angiogenesis bone vascularization |
url | https://www.mdpi.com/1660-3397/19/4/194 |
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