A comparative study of brain tumor cells from different age and anatomical locations using 3D biomimetic hydrogels

ABSTRACT Brain tumors exhibit vast genotypic and phenotypic diversity depending on patient age and anatomical location. Hydrogels hold great promise as 3D in vitro models for studying brain tumor biology and drug screening, yet previous studies were limited to adult glioblastoma cells, and most studies used immortalized cell lines. Here we report a hydrogel platform that supports the proliferation and invasion of patient-derived brain tumor cell cultures (PDCs) isolated from different patient age groups and anatomical locations. Hydrogel stiffness was tuned by varying poly(ethylene-glycol) concentration. Cell adhesive peptide (CGRDS), hyaluronic acid, and MMP-cleavable crosslinkers were incorporated to facilitate cell adhesion and cell-mediated degradation. Three PDC lines were compared including adult glioblastoma cells (aGBM), pediatric glioblastoma cells (pGBM), and diffuse pontine intrinsic glioma (DIPG). A commonly used immortalized adult glioblastoma cell line U87 was included as a control. PDCs displayed stiffness-dependent behavior, with 40 Pa hydrogel promoting faster tumor proliferation and invasion. Adult GBM cells exhibited faster proliferation than pediatric GBM, and DIPG showed slowest proliferation. These results suggest both patient age and tumor location affects brain tumor behaviors. Adult GBM PDCs also exhibited very different cell proliferation and morphology from U87. The hydrogel reported here can provide a useful tool for future studies to better understand how age and anatomical locations impacts brain tumor progression using 3D in vitro models.