title: Laminin promotes vascular network formation in 3D in vitro collagen scaffolds by regulating VEGF uptake.
abstract: Angiogenesis is an essential neovascularisation process, which if recapitulated in 3D in vitro, will provide better understanding of endothelial cell (EC) behaviour. Various cell types and growth factors are involved, with vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2 key components. We were able to control the aggregation pattern of ECs in 3D collagen hydrogels, by varying the matrix composition and/or having a source of cells signalling angiogenic proteins. These aggregation patterns reflect the different developmental pathways that ECs take to form different sized tubular structures. Cultures with added laminin and thus increased expression of α6 integrin showed a significant increase (p<0.05) in VEGFR2 positive ECs and increased VEGF uptake. This resulted in the end-to-end network aggregation of ECs. In cultures without laminin and therefore low α6 integrin expression, VEGFR2 levels and VEGF uptake were significantly lower (p<0.05). These ECs formed contiguous sheets, analogous to the 'wrapping' pathway in development. We have identified a key linkage between integrin expression on ECs and their uptake of VEGF, regulated by VEGFR2, resulting in different aggregation patterns in 3D.
authors.affiliation: University College London Tissue Repair and Engineering Centre, Institute of Orthopaedics and Musculoskeletal Sciences, Division of Surgery and Interventional Science, Stanmore Campus HA7 4LP, United Kingdom.
authors.forename: Katerina
authors.initials: K
authors.lastname: Stamati
authors.affiliation: Centre for Neuroscience & Trauma, Blizard Institute of Cell and Molecular Science Barts and The London School of Medicine and Dentistry, 4 Newark Street Whitechapel London E1 2AT, United Kingdom.
authors.forename: John V
authors.initials: JV
authors.lastname: Priestley
authors.affiliation: University College London Tissue Repair and Engineering Centre, Institute of Orthopaedics and Musculoskeletal Sciences, Division of Surgery and Interventional Science, Stanmore Campus HA7 4LP, United Kingdom.
authors.forename: Vivek
authors.initials: V
authors.lastname: Mudera
authors.affiliation: University College London Tissue Repair and Engineering Centre, Institute of Orthopaedics and Musculoskeletal Sciences, Division of Surgery and Interventional Science, Stanmore Campus HA7 4LP, United Kingdom. Electronic address: u.cheema@ucl.ac.uk.
authors.forename: Umber
authors.initials: U
authors.lastname: Cheema
mesh_terms: D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D039503:Integrin alpha6 / Q000378:metabolism; D007797:Laminin / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D039503:Integrin alpha6; D007797:Laminin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Angiogenesis; Collagen; Endothelial cells; Integrin; Laminin; Receptors; VEGF