Biomedical Engineering Reference
In-Depth Information
Tubulogenic assays can be obtained using different experimental set-ups,
substrata (e.g., Matrigel, fibronectin, collagen, fibrin, semisolid methilcellu-
lose), and endothelial cell-lines (e.g., human umbilical vein endothelial cells
(HUVECs), human dermal microvascular endothelial cells (HDMECs), human
capillary endothelial cells (HCECs), human marrow microvascular endothelial
cells, bovine aorthic endothelial cells (BAECs), bovine capillary endothelial
cells (BCECs), bovine retin endothelial cells (BRECs), rat capillary endothe-
lial cells (RCECs), embryonic stem cells (ESCs), calf pulmonary aortic en-
dothelial cells (CPAECs), adrenal capillary endothelial cells (ACECs)).
In particular, an increasing number of vasculogenic experiments has been
recently performed with tumor-derived endothelial cells (TECs): laboratory
investigations have in fact demonstrated that, according to a macroscopic
morphological analysis, tumor blood vessels are irregular and dilated and the
vessel hierarchy is not well defined, so that distinct venules, arterioles, and
capillaries are undistinguishable [100, 148]. Moreover, they differ from their
\normal" counterpart by altered blood ow and permeability, and by abnor-
malities in pericytes and in the basement membrane. Therefore, as also seen in
the previous chapter, vascular endothelial cells deriving from tumors (TECs)
represent a more adequate model for studying the mechanisms of malignant
vascularization [21, 54, 170].
In spite of such a large variety of laboratory protocols mentioned above,
it is possible to point out a unified illustration of the common features of
the experimental process. The selected EC population is initially dispersed in
a physiological solution and then poured on the top of a specific substrate,
which typically favors cell motility and has biochemical characteristics similar
to living tissues. The cells sediment by gravity onto the surface and then move
on it, giving rise to the mechanisms of aggregation and pattern formation. In
more detail, the overall process, which commonly lasts 9{15 h, consists of the
following steps:
1. Cells initially undergo an isotropic motion around their initial position,
maintaining a round shape. Then, it seems that they choose a direction,
which is correlated with the location of areas characterized by higher
cellular densities, and display an independent migration, with a small
random component, until they collide with their closest neighbors (3{
6 h). This motile phenotype is called in biology cell persistence and
is related to the inertia of a cell in rearranging and repolarizing its
cytoskeleton, maintaining its own direction of migration.
2. After collision, ECs attach to their neighbors eventually forming a con-
tinuous and structure multicellular network, which can be represented
as a collection of nodes connected by capillary chords (see Figure 7.1).
3. The network slowly moves as a whole, undergoing a slow thinning pro-
cess, which however leaves the structure mainly unaltered.
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