Laminin promotes vascular network formation in 3D in vitro collagen scaffolds by regulating VEGF uptake

被引:66
作者
Stamati, Katerina [1 ]
Priestley, John V. [2 ]
Mudera, Vivek [1 ]
Cheema, Umber [1 ]
机构
[1] Univ Coll London, Tissue Repair & Engn Ctr, Inst Orthopaed & Musculoskeletal Sci, Div Surg & Intervent Sci, Stanmore HA7 4LP, Middx, England
[2] Barts & London Queen Marys Sch Med & Dent, Blizard Inst Cell & Mol Sci, Ctr Neurosci & Trauma, London E1 2AT, England
基金
英国生物技术与生命科学研究理事会;
关键词
Endothelial cells; Angiogenesis; VEGF; Receptors; Integrin; Collagen; Laminin; MESENCHYMAL STEM-CELLS; HUMAN-ENDOTHELIAL CELLS; MARROW STROMAL CELLS; CAPILLARY MORPHOGENESIS; BASEMENT-MEMBRANE; TUBE FORMATION; ANGIOGENESIS; DIFFERENTIATION; COCULTURES; STIMULATE;
D O I
10.1016/j.yexcr.2014.05.012
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 alpha 6 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 alpha 6 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. (C) 2014 The Authors. Published by Elsevier Inc.
引用
收藏
页码:68 / 77
页数:10
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