Glioblastoma multiforme (GBM), an aggressive brain tumor, represents one of the most incurable human cancers due to its highly invasive nature. GBM tumors are highly heterogeneous that are composed of tumor cells and small portion of tumor initiating cells also known as glioblastoma stem cells (GSCs) that contribute to the therapeutic resistance and tumor recurrence following surgery. For improving the therapeutic efficiency, targeting GSCs and their surrounding microenvironment appears to be a promising approach. The tumor microenvironment provides physical, chemical and cellular cues that nurture the stemness properties of the GSCs and thus promote tumorigenesis, therapeutic resistance and tumor recurrence. A mechanistic understanding of the impact of these microenvironmental cues on GSCs is crucial in developing an efficient therapeutic approach. Here, we employed three dimensional (3D) hyaluronic acid (HA) hydrogels that allow incorporation of brain microenvironment cues to investigate GSC behaviors. In this study, U87 cell line and patient derived D456 cells were cultured adherently (in the presence of serum) and/or as suspension culture (serum-free) and were then encapsulated in HA hydrogels. We observed that all the seeded single cells expanded and formed spheres, and size of the spheres increased with time. Increasing the initial cell seeding density of cells influenced the sphere size distribution. Interestingly, clonal expansion of serum-free grown tumor cells in HA hydrogels was observed. Also, stemness marker expression of serum and/or serum-free grown cells was altered when cultured in HA hydrogels. Next, we hypothesized that the niche cells in the brain environment when cultured together with the GSCs enhance their stemness phenotype. To test this, we are currently investigating the impact of astrocytes and/or endothelial cells in our 3D HA model in different cell seeding densities. Overall, such biomimetic culture systems could further our understanding of microenvironmental regulation of GSC phenotypes.

Investigating glioblastoma stem cell behaviors in three-dimensional hyaluronic acid hydrogels

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.