Department of Metabiohealth, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea.
School of Mechanical Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea.
Biosensors (Basel). 2024 Nov 7;14(11):539. doi: 10.3390/bios14110539.
Glioblastoma multiforme (GBM) is among the most aggressive brain cancers, and it contains glioma stem cells (GSCs) that drive tumor initiation, progression, and recurrence. These cells resist conventional therapies, contributing to high recurrence rates in GBM patients. Developing in vitro models that mimic the tumor microenvironment (TME), particularly the GSC niche, is crucial for understanding GBM growth and therapeutic resistance. Three-dimensional (3D) spheroid models provide a more physiologically relevant approach than traditional two-dimensional (2D) cultures, recapitulating key tumor features like hypoxia, cell heterogeneity, and drug resistance. This review examines scaffold-free and scaffold-based methods for generating 3D GBM spheroids, focusing on their applications in studying the cancer stem cell niche. The discussion encompasses methods such as the hanging drop, low-adhesion plates, and magnetic levitation, alongside advancements in embedding spheroids within extracellular matrix-based hydrogels and employing 3D bioprinting to fabricate more intricate tumor models. These 3D culture systems offer substantial potential for enhancing our understanding of GBM biology and devising more effective targeted therapies.
多形性胶质母细胞瘤（GBM）是最具侵袭性的脑癌之一，其中包含驱动肿瘤起始、进展和复发的神经胶质瘤干细胞（GSCs）。这些细胞抵抗传统疗法，导致 GBM 患者的复发率居高不下。开发能够模拟肿瘤微环境（TME），特别是 GSC 生态位的体外模型，对于理解 GBM 的生长和治疗抵抗至关重要。三维（3D）球体模型比传统的二维（2D）培养更能提供生理相关性的方法，重现了缺氧、细胞异质性和耐药性等关键肿瘤特征。本综述探讨了无支架和有支架方法来生成 3D GBM 球体，重点介绍了它们在研究癌症干细胞生态位中的应用。讨论包括悬滴、低黏附板和磁悬浮等方法，以及将球体嵌入细胞外基质基水凝胶中的进展，以及使用 3D 生物打印来制造更复杂的肿瘤模型。这些 3D 培养系统为增强我们对 GBM 生物学的理解和设计更有效的靶向治疗提供了巨大的潜力。
