Tissue Engineered Models of Brain Tumors and Their Applications

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medicine, mathematical modeling, dissecting the cellular and molecular na-

ture of the tumor for basic research are keys to address challenges to find a

cure.

Since diversity and changes in cellular and extracellular environments are

primary mediators between pre-clinical tissue engineering models and clinical

trials for brain tumors, GBM microenvironment will be highlighted to under-

stand the sources and contribution of cellular and molecular heterogeneity in

this chapter. Non-cellular components of this 3D network will also be summa-

rized, as they are key players to develop innovative in vitro mimics of tumor

tissue. A detailed analysis will further be performed on GBM models in tissue

engineering with their current applications.

3.2

Glioblastoma (GBM) Microenvironment

In GBM, tumor and its growth are not isolated, as they include a complex

interplay between cellular and non-cellular components contributed by signif-

icant changes in tissue organization, interactions and signaling. This environ-

ment is assembled with cancer cells and cancer stem cells, tissue resident cells,

infiltrating immune system cells and vasculature. Besides, non-cellular compo-

nents are crucial, as they play a pivotal role in tumor progression and therapy.

Thus, our current understanding of this crosstalk is of utmost importance to

the onset, progression and prognosis of GBM as well as is a key hallmark to

establish diverse treatment and tissue-engineered model strategies to improve

clinical outcomes. This 3D non-cellular network of tumor environment is built

with extracellular matrix (ECM), soluble signals and their gradients [3, 4]. In

this section, an overview of these cellular and non-cellular constituents of GBM

microenvironment, as well as their essential tasks for tumor and tumor-model

reconstruction will be provided.

3.2.1

Cellular Environment and Signals of GBM

GBM onset and progression modify the content of the relevant brain tissue in

a unique pattern. In this tumor, cancer cells, cancer stem cells, tissue-resident

cells, resident and migrating immune system cells, and brain vasculature are

the major cells/cell sources in tumor mass or in the surrounding tissue. Ad-

ditionally, interface between brain and blood circulation is built with blood-

brain barrier (BBB) that contributes to both healthy brains as well as the

development of related diseases [3, 4].

3.2.1.1

Cancer Cells, Cancer Stem Cells (CSCs)

Currently, cell of origin for GBM is largely unknown, but it has been con-

sidered that neural stem cells, astrocytes, oligodendrocyte precursor cells and