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Brain-Mimetic, Three-Dimensional Hyaluronic Acid-Based Hydrogels to Investigate Effects of the Tumor Microenvironment on Glioblastoma Progression

  • Author(s): Sohrabi, Alireza
  • Advisor(s): Seidlits, Stephanie
  • et al.
Abstract

Glioblastoma (GBM) is the most common and lethal type of brain cancers with median survival of 12-15 months. The poor patient prognosis is partially due to the highly infiltrative nature of GBM. GBM cells invasion through brain parenchyma is the main reason for secondary tumor formation. We posit that the unique brain extracellular matrix (ECM) facilitates GBM invasion. Specifically, we focused on the perivasculature niche surrounding the GBM tumor and the biophysical properties of the tumor. To study these, we fabricated a brain-mimetic, three-dimensional hydrogel platform based on hyaluronic acid (HA) with orthogonal control on biochemical and biophysical properties. First, we used this platform to study the crosstalk between GBM cells and the perivasculature. We found that cells derived from perivascular niche of GBM patient tumors induced a migratory phenotype in patient-derived GBM cells. Second, mimicking biophysical properties of a GBM tumor within the HA hydrogel platform enabled us to demonstrate that the ECM stiffness directly caused a switch in GBM metabolism pathway. By using this novel in vitro platform, we were able to uncover effects of the ECM on GBM progression which have not been observable with traditional methods.

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