Computational models for generating microvascular structures: Investigations beyond medical imaging resolution

Abstract

Angiogenesis, arteriogenesis, and pruning are revascularization processes essential to our natural vascular development and adaptation, as well as central players in the onset and development of pathologies such as tumoral growth and stroke recovery. Computational modeling allows for repeatable experimentation and exploration of these complex biological processes. In this review, we provide an introduction to the biological understanding of the vascular adaptation processes of sprouting angiogenesis, intussusceptive angiogenesis, anastomosis, pruning, and arteriogenesis, discussing some of the more significant contributions made to the computational modeling of these processes. Each computational model represents a theoretical framework for how biology functions, and with rises in computing power and study of the problem these frameworks become more accurate and complete. We highlight physiological, pathological, and technological applications that can be benefit from the advances performed by these models, and we also identify which elements of the biology are underexplored in the current state‐of‐the‐art computational models. This article is categorized under: Cancer > Computational Models Cardiovascular Diseases > Computational Models

Computational modeling of angiogenesis: The importance of cell rearrangements during vascular growth

“…We also mention if model simulations were compared to experimental data (if nothing is stated, then no comparison to experiments was carried out). For alternative reviews of the existing literature on mathematical and computational (snail‐trail) models of angiogenesis, we refer the reader to the reviews of Scianna et al (2013), Vilanova et al (2017a), Mantzaris et al (2004), Heck et al (2015), Peirce (2008), and Apeldoorn et al (2022). Other reviews, with a more specialized focus, include the work by Flegg et al on wound‐healing and tumor‐induced angiogenesis (Flegg et al, 2020; includes a timeline indicating significant modeling works in this context), reviews from a systems biology perspective (Logsdon et al, 2013; Zhang et al, 2021), and multiscale models of angiogenesis (Qutub et al, 2009).…”

“…However, most existing theoretical models of angiogenesis neglect phenotype‐dependent behaviors of individual ECs, such as cell rearrangements, and instead use a coarser, snail‐trail description of sprouting (see later in Section 3). Although mathematical and computational models of angiogenesis have been extensively reviewed (e.g., Apeldoorn et al, 2022; Heck et al, 2015; Mantzaris et al, 2004; Peirce, 2008; Scianna et al, 2013; Vilanova et al, 2017a), this is the first review focusing on cell rearrangements during early angiogenic sprouting. In particular, we review snail‐trail and cell‐mixing models of angiogenesis (see also Figure 2 and Table 1) and discuss when the effects of cell rearrangements on vascular morphology cannot be neglected.…”

Prostate Cancer Microvascular Routes: Exploration and Measurement Strategies

“…Pruning constitutes a fundamental process occurring at all levels of the vascular network, serving as a remodeling mechanism aimed at reducing the energetic demands associated with tissue perfusion [99,100]. Unlike sprouting, which emerges as a cellular response to localized needs, pruning is thought to have evolved as a strategy to minimize the energy required for blood flow.…”

“…Unlike sprouting, which emerges as a cellular response to localized needs, pruning is thought to have evolved as a strategy to minimize the energy required for blood flow. This optimization is achieved by restructuring the existing vascular network to reduce its overall length and surface area, yet without compromising its essential functionality [99]. While the criteria for selecting specific vessel segments for pruning remain ambiguous, the general sequence in developmental remodeling involves ECs constricting the vessel.…”

“…Several plausible explanations for these discordant findings have been proposed. These include variations in the methodologies employed for counting micro-vessels, inconsistencies in the types of antibodies utilized, disparities in the sizes of the populations studied, and divergent levels of expertise and pathological understanding among researchers [99].…”