title: Quantification of angiogenic sprouting under different growth factors in a microfluidic platform.
abstract: 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, TGFβ 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 monolayer 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. TGFβ 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.
authors.affiliation: Multiscale in Mechanical and Biological Engineering (M2BE), Aragón Institute of Engineering Research (I3A), Department of Mechanical Engineering, University of Zaragoza, Zaragoza, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Del Amo
authors.affiliation: Multiscale in Mechanical and Biological Engineering (M2BE), Aragón Institute of Engineering Research (I3A), Department of Mechanical Engineering, University of Zaragoza, Zaragoza, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Borau
authors.affiliation: Multiscale in Mechanical and Biological Engineering (M2BE), Aragón Institute of Engineering Research (I3A), Department of Mechanical Engineering, University of Zaragoza, Zaragoza, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Gutiérrez
authors.affiliation: Department of Statistical Methods, University of Zaragoza, Zaragoza, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Asín
authors.affiliation: Multiscale in Mechanical and Biological Engineering (M2BE), Aragón Institute of Engineering Research (I3A), Department of Mechanical Engineering, University of Zaragoza, Zaragoza, Spain. Electronic address: jmgaraz@unizar.es.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: García-Aznar
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology*; D006801:Humans; D044085:Microfluidics; D018919:Neovascularization, Physiologic; D010982:Platelet-Derived Growth Factor / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; Collective Cell Migration; Growth factors; Microfluidics; Sprouting