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Bioinformatics of the Brain

3.3

In vitro Experimental GBM Mimics

In traditional practice, cells are isolated, cultured and manipulated as 2D

monolayers. Yet, in the recent decades, there has been increasing concern on

whether these systems reflect the native organization or they are mere artifacts

of the body. This doubt has risen on the ground of analysis on the mechani-

cal, chemical and biological discrepancy between 2D culture and multicellular

body organization. Typically, 2D culture presents higher stiffness and near

uniform chemical factor distribution, induces cellular polarity with monolayer

spreading, and restricts cell-cell communication as well as organization. Con-

versely, 3D ECM accommodates for various interactions in a chemical-gradient

environment, is dynamically remodeled and manages cellularity, morphologi-

cal, translational and behavioral modifications of cells harbored. When these

3D culture systems are designed to possess time-controlled properties that

respond to external stimuli, various aspects of physiological and pathological

state of the tissues and organs can be uncovered [120, 121].

3.3.1

2D Models

Although 2D monolayer systems as gold standards are devoided of certain

features of the body, they significantly contributed to the advancement of to-

day’s research. This approach is still in practice and invaluable tool to meet

the demand to supply specific amount of cells for diverse set of applications.

Their common utilization as pre-clinical models is attributed to their low cost,

simplicity, and ease of maintenance [122], yet they fail to sustain important

characteristics such as cellular and genetic heterogeneity, and microenviron-

ment of tumors. These drawbacks led to unreliable drug efficacy and modeling

data in clinics [123, 124].

3.3.2

2.5D Models

Standard bare tissue culture polystyrene surfaces were dominant in cancer

studies in pre-clinical research for several decades, but biomaterial coated-

plastic or -glass surfaces are increasingly employed to study tumors as pre-

clinical 2.5D models. These coated surfaces can be modified with ECM derived

proteins such as collagen I and laminin, with ECM mimics such as matrigel

and decellularized ECM, or with adhesion ligands such as RGD [125–129].

In 2.5D models, micropatterned and nanofiber substrates can provide phys-

iologically relevant topological ECM cues as described in previous reports. In

a recent study, electrospun polystyrene fibers were tuned to analyze direc-

tionality of U87 single cell migration in motility assays [130]. Additionally,

U87 cells on electrospun suspended gelatin mesofibers displayed aggregation,

deformation, and migration dynamics [131] and poly(vinyl alcohol) coated sil-