Biomedical Engineering Reference
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FIGURE 7.2: Effect of VEGF-induced calcium signals in the process of in
vitro vasculogenesis. The accumulation of the ion triggers motility, chemical
response, adhesion and cytoskeletal reorganization of TECs, crucial events
for the capillary-like network formation. The specific pathways involved in
cytosolic calcium entry are reproduced in Figure 6.1.
4. Finally, individual cells fold up to origin the lumen of the capillary, so
that the resulting vascular network forms along the lines of the previous.
The early patterning is complete in a characteristic time suciently distant
from critical events, such as cell mitosis or death, that allows to assume the
cell density conserved. The final structure is no longer substantially modi-
fied and resembles a primitive in vivo capillary-like plexus [133]. The overall
process is largely mediated by the redundant activity of multiple chemical
morphogens (such as vascular endothelial growth factor isoforms, acidic and
basic fibroblast growth factors, epidermal growth factor, transforming growth
factor-, transforming growth factor- and several more, as reviewed in [128])
that, behaving as signal exchangers signals by their release and absorption,
exert a chemotactic action and, concomitantly, activate both in normal ECs
and in tumor-derived individuals a series of calcium-dependent cascades, reg-
ulating cells phenotypical behavior as already seen in Chapter 6 and described
in [134, 216, 274, 276, 277, 282, 283, 366] and in the references therein (Figure
7.2).
The analysis performed on the tubulogenic system and on its driving
molecular mechanisms has revealed the role of different factors operating in
malignant vascular progression. However, innumerable other component pro-
cesses, acting at different scales, are far from being completely elucidated. In
particular, their complexity presents a number of components that could be in
principle interfered in multiple ways to inhibit malignant vascular progression.
This large combinatorial space of possible therapies is obviously unfeasible to
search using only laboratory-based biological methods. A modeling approach
able to replicate selected features of an in vitro TEC tubulogenesis is therefore
useful in this respect.
Indeed, in this chapter, the CPM used in the previous chapter to simulate
the motility assay of the individual tumor-derived endothelial cell is extended
to the multicellular situation, including cross-talk among cells. The proposed
 
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