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2D cell-culture models with a monolayer on standard microplates are the most widely used method for drug screening due to significant advantages, such as simplicity, low-cost, high throughput 63 However, 2D cell-culture models fail to recapitulate the physiology of the tumor, which is known to drastically affect drug responses 64,65,66 In contrast, self-organized 3D spheroids better mimic the physical and biochemical features of a solid tumor by including cell-cell adhesion and interaction and cell-extracellular matrix interactions 64,67,68 3D cell culturing is particularly relevant for DMG cells, which are often maintained in suspension culture as neurospheres, as 3D methods have been shown to support cancer stem cell proliferation 66,69,70 However, most 3D brain-tumor models still lack an essential physiological component, which greatly affects treatment outcome and disease progression, namely the active microvasculature, which strongly limits drug delivery 13,71,72