Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China.
Colloids Surf B Biointerfaces. 2018 Nov 1;171:629-637. doi: 10.1016/j.colsurfb.2018.08.006. Epub 2018 Aug 7.
Glioblastoma (GBM), with rich blood vessels and high invasiveness, is the most common malignant primary brain tumor. The current treatment strategies are less effective, resulting in tumor recurrence. Tumor angiogenesis plays an important role in the occurrence, development and metastasis of GBM. Currently, GBM has been treated by inhibiting tumor angiogenesis. In-depth study of tumor angiogenesis is of great significance for the treatment of GBM. Recent studies have shown that glioma stem cells (GSCs) are involved in tumor vascularization by secreting vascular endothelial growth factor (VEGF). It is necessary to construct an ideal in vitro model to study the mechanism of GSCs in tumor vascularization. Here we used extrusion-based three-dimensional (3D) bioprinting technology to fabricate GSCs tumor model. In this study, the viability of cells after bioprinting was 86.27 ± 2.41%. Furthermore, compared with traditional suspension culture, the proliferation of 3D printed GSCs was more stable. Through the transmission electron microscopy (TEM), numerous long microvilli of cells cultured in 3D bioprinted scaffolds were observed. 3D bioprinted GSCs also have more abundant mitochondria and rough endoplasmic reticulum. Additionally, the stemness properties, the expression of tumor angiogenesis-related genes and vascularization potential of 3D bioprinted GSCs in vitro were higher than that of suspension cultured cells. In summary, 3D bioprinted cell-laden hydrogel scaffolds provide a proper model for investigating the biological characteristics of GSCs and tumor angiogenesis.
胶质母细胞瘤（GBM）血管丰富，侵袭性高，是最常见的恶性原发性脑肿瘤。目前的治疗策略效果不佳，导致肿瘤复发。肿瘤血管生成在 GBM 的发生、发展和转移中起着重要作用。目前，GBM 已通过抑制肿瘤血管生成进行治疗。深入研究肿瘤血管生成对 GBM 的治疗具有重要意义。最近的研究表明，神经胶质瘤干细胞（GSCs）通过分泌血管内皮生长因子（VEGF）参与肿瘤血管生成。有必要构建理想的体外模型来研究 GSCs 在肿瘤血管生成中的机制。在这里，我们使用基于挤出的三维（3D）生物打印技术来构建 GSCs 肿瘤模型。在这项研究中，生物打印后细胞的存活率为 86.27 ± 2.41%。此外，与传统的悬浮培养相比，3D 打印的 GSCs 增殖更稳定。通过透射电子显微镜（TEM）观察到培养在 3D 生物打印支架中的细胞有许多长微绒毛。3D 生物打印的 GSCs 还具有更丰富的线粒体和粗糙内质网。此外，3D 生物打印的 GSCs 的干性特征、肿瘤血管生成相关基因的表达和血管生成潜力均高于悬浮培养的细胞。总之，3D 生物打印的细胞负载水凝胶支架为研究 GSCs 的生物学特性和肿瘤血管生成提供了合适的模型。
