Glioblastoma is the most frequently diagnosed primary malignant brain tumor with unfavourable prognosis and high mortality. One of its key features is the extensive abnormal vascular network. Up to now, the mechanism of angiogenesis and the origin of tumor vascularization remain controversial. It is essential to establish an ideal preclinical tumor model to elucidate the mechanism of tumor vascularization, and the role of tumor cells in this process. In this study, both U118 cell and GSC23 cell exhibited good printability and cell proliferation. Compared with 3D‐U118, 3D‐GSC23 had a greater ability to form cell spheroids, to secrete vascular endothelial growth factor (VEGFA), and to form tubule‐like structures in vitro. More importantly, 3D‐glioma stem cells (GSC)23 cells had a greater power to transdifferentiate into functional endothelial cells, and blood vessels composed of tumor cells with an abnormal endothelial phenotype was observed in vivo. In summary, 3D bioprinted hydrogel scaffold provided a suitable tumor microenvironment (TME) for glioma cells and GSCs. This bioprinted model supported a novel TME for the research of glioma cells, especially GSCs in glioma vascularization and therapeutic targeting of tumor angiogenesis.

中文翻译：

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用于胶质瘤血管化的 3D 生物打印胶质瘤微环境

胶质母细胞瘤是最常见的原发性恶性脑肿瘤，预后不良，死亡率高。其主要特征之一是广泛的异常血管网络。迄今为止，血管生成的机制和肿瘤血管化的起源仍存在争议。建立理想的临床前肿瘤模型对于阐明肿瘤血管化的机制以及肿瘤细胞在这一过程中的作用至关重要。在这项研究中，U118 细胞和 GSC23 细胞都表现出良好的可印刷性和细胞增殖能力。与 3D-U118 相比，3D-GSC23 在体外形成细胞球体、分泌血管内皮生长因子 (VEGFA) 和形成小管样结构的能力更强。更重要的是，3D 神经胶质瘤干细胞 (GSC)23 细胞具有更强的转分化为功能性内皮细胞的能力，在体内观察到由具有异常内皮表型的肿瘤细胞组成的血管。总之，3D 生物打印水凝胶支架为神经胶质瘤细胞和 GSC 提供了合适的肿瘤微环境 (TME)。这种生物打印模型支持了一种新的 TME，用于研究胶质瘤细胞，特别是胶质瘤血管化中的 GSCs 和肿瘤血管生成的治疗靶向。