Journal
JOURNAL OF BIOMECHANICS
Volume 49, Issue 8, Pages 1340-1346Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.jbiomech.2015.10.026
Keywords
Sprouting; Angiogenesis; Growth factors; Microfluidics; Collective Cell Migration
Categories
Funding
- European Research Council (ERC) [ERC-2012-StG 306751]
- Spanish Ministry of Economy and Competitiveness [DPI2012-38090-C03-01]
- Ministry of Education, Culture and Sports, Spain [FPU13/03194]
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Angiogenesis, as example of collective migration of endothelial cells (ECs), is the main dynamic process that culminates in sprout formation from existing vessels. After tissue injury, the vascularity is interrupted, triggering the regeneration process and the release of different growth factors (GFs). The main aim of this work is to quantify the effect of specific GFs during the initial stage of sprout formation, namely: VEGF, PDGF-BB, TGF beta and BMP-2, all of them involved in regenerative processes. For this purpose, we designed a novel algorithm implemented in Matlab to quantify the advance of the EC mono layer over time and the sprout structure in 3D. Our results show that VEGF is the main regulatory GF on angiogenesis processes, producing longer sprouts with higher frequency. However, the chemoattractant effect of VEGF depends on its concentration and its spatiotemporal location, having a critical impact on the sprout time evolution. PDGF-BB (namely as PDGF) has a global negative effect on both the number and length of sprouts. TGF beta enhances sprout length at earlier times, although its effect gradually disappears over time. Finally, BMP-2 produces, overall, less number and shorter sprouts, but was the only GF with a positive evolution at longer times, producing fewer but longer sprouts. (C) 2015 Elsevier Ltd. All rights reserved.
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