Effects of endothelial cell proliferation and migration rates in a computational model of sprouting angiogenesis

Abstract

Angiogenesis, the recruitment of new blood vessels, is a critical process for the growth, expansion, and metastatic dissemination of developing tumors. Three types of cells make up the new vasculature: tip cells, which migrate in response to gradients of vascular endothelial growth factor (VEGF), stalk cells, which proliferate and extend the vessels, and phalanx cells, which are quiescent and support the sprout. In this study we examine the contribution of tip cell migration rate and stalk cell proliferation rate on the formation of new vasculature. We calculate several vascular metrics, such as the number of vascular bifurcations per unit volume, vascular segment length per unit volume, and vascular tortuosity. These measurements predict that proliferation rate has a greater effect on the spread and extent of vascular growth compared to migration rate. Together, these findings provide strong implications for designing anti-angiogenic therapies that may differentially target endothelial cell proliferation and migration. Computational models can be used to predict optimal anti-angiogenic therapies in combination with other therapeutics to improve outcome.

A computational multiscale agent-based model for simulating spatio-temporal tumour immune response to PD1 and PDL1 inhibition

“…A dynamic tumour vasculature module coupled with tumour perfusion should be able to capture tumour development in a more mechanistic manner. The vascular geometry could either be taken from experiments [ 60 ] or from computational models [ 38 , 61 ]. At an organ-system scale, events including CD8 + T-cell priming (in the lymph node), trafficking (via blood circulation) and recruitment to the tumour compartment are largely simplified and phenomenological.…”

Hydrogen sulfide improves postischemic neoangiogenesis in the hind limb of cystathionine-β-synthase mutant mice via PPAR-γ/VEGF axis

“…Neoangiogenesis is a natural process during chronic regional ischemia, which requires EC proliferation, migration, differentiation, and survival to form new blood vessels in order to compensate the hypoxic environment (Norton and Popel 2016). VEGF is a prototypical angiogenic cytokine that plays a vital role in this process and has been widely studied (Carmeliet 2000;Isner and Asahara 1999;Liu et al 2000).…”

Integration of in vitro and in silico Models Using Bayesian Optimization With an Application to Stochastic Modeling of Mesenchymal 3D Cell Migration

“…In fact, these computational models can be classified according to several factors such as the numerical approach of the biological processes: continuous (Vermolen and Javierre, 2012 ; Valero et al, 2014b ; Serrano-Alcalde et al, 2017 ), discrete (Meineke et al, 2001 ; Bentley et al, 2009 ; Scianna et al, 2012 ; Scianna and Preziosi, 2014 ; Van Liedekerke et al, 2015 ), or hybrid (Alber et al, 2007 ; Bauer et al, 2009 ; Daub and Merks, 2013 ; Milde et al, 2014 ; González-Valverde and García-Aznar, 2018 ). In addition, they can also be classified according to the type of movement that cells develop as individual (Schlüter et al, 2012 ; Trichet et al, 2012 ; Ribeiro et al, 2017 ; Moure and Gomez, 2018 ), if cells migrate independently, or collective, forming an interconnected meshwork or cluster (Bazmara et al, 2015 ; González-Valverde et al, 2016 ; Norton and Popel, 2016 ; Camley and Rappel, 2017 ; Escribano et al, 2018 ). Computational models can also be classified as mechanical (Zaman et al, 2005 ; Borau et al, 2011 ), biochemical (Hatakeyama et al, 2003 ; Provenzano et al, 2008 ), or mechano-chemical (Kim et al, 2015 , 2018 ; Moure and Gomez, 2017 ; Ribeiro et al, 2017 ).…”