Angi-13. Recapitulating the Glioblastoma Perivascular Niche Through Patient-Derived Tumor-Vascular Spheroid Co-Culture

The perivascular niche plays a crucial role in glioblastoma (GBM) progression and therapy resistance. However, recapitulating the dynamic interaction between GBM cells and human blood vessels remains a challenge in preclinical models. In this study, we utilized patient-derived GBM tissues and engineered vascular spheroids to establish an in vitro platform for studying tumor–vascular interactions. Vascular spheroids were generated from primary human endothelial cells and co-cultured with patient-derived GBM tissues or dissociated tumor organoids. Morphological changes, vessel infiltration, and spatial associations were analyzed using immunofluorescence and 3D confocal microscopy. Expression of angiogenic and stemness markers (PDGFRβ, CD31, Nestin, OLIG2) was assessed via qPCR and immunostaining. GBM tissues exhibited directional migration toward vascular spheroids and induced vessel sprouting and reorganization. Confocal analysis revealed close association of GBM cells with endothelial networks, mimicking perivascular niche characteristics. Molecular profiling indicated upregulation of angiogenesis-associated markers in the co-culture model compared to monoculture controls. Our in vitro co-culture platform effectively models the vascular–GBM interface, enabling mechanistic studies on perivascular invasion and vessel co-option. This system holds potential for screening anti-angiogenic and anti-invasive therapeutics in a patient-specific context.