用类器官模拟胶质瘤：为转化神经肿瘤学重建人类神经微环境
Modeling gliomas with organoids: reconstructing the human neural microenvironment for translational neuro-oncology.
摘要(中文译文)
胶质瘤是中枢神经系统中最致命且生物学上最复杂的肿瘤之一，在成人和儿童人群中均预后不良。除肿瘤内在的遗传改变外，越来越多的证据表明胶质瘤的进展是由与神经微环境的动态相互作用所驱动的，尤其是通过肿瘤与神经元的直接通讯。利用单细胞图谱分析和多组学技术对成人和儿童胶质瘤（包括胶质母细胞瘤（GBM）和弥漫性中线胶质瘤（DMG））的研究揭示了广泛的肿瘤内在和外在异质性，具有表型和遗传可塑性的肿瘤细胞与神经元、胶质细胞、血管系统和免疫区室 actively 相互作用，共同重塑神经微环境以促进肿瘤生长、侵袭和治疗耐药。传统的二维培养系统和动物模型无法完全再现这些相互作用，限制了机制性认识并将临床转化至人类患者的能力受到制约。近年来类器官技术的进展弥补了这一空白，使得开发胶质瘤-微环境相互作用的三维人类特异性模型成为可能。iPSC来源的脑类器官、区域模式化神经类器官、患者来源的胶质瘤类器官以及肿瘤-类器官共培养系统等平台捕获了这些人类疾病的基本特征。这些系统再现了肿瘤-神经元突触整合、弥漫性侵袭程序、活动依赖性肿瘤生长、缺氧结构化生态位、血管相互作用以及患者特异性治疗反应。在本综述中，我们综合了胶质瘤类器官模型系统的最新进展和生物学见解，并评估了其优势和局限性，包括神经血管和多谱系系统。我们进一步强调了新兴的创新技术，这些技术增强了这些模型的生理保真度、可重复性和可扩展性。总体而言，这些平台确立了肿瘤微环境相互作用作为胶质瘤生物学的核心组织原则，并为机制发现、治疗开发和个性化神经肿瘤学提供了坚实的基础。
Abstract
Gliomas represent some of the most lethal and biologically complex tumors of the central nervous system, with poor outcomes across both adult and pediatric populations. Beyond tumor-intrinsic genetic alterations, glioma progression is increasingly recognized to be driven by dynamic interactions with the neural microenvironment, particularly through direct tumor-neuron communication. Studies of adult and pediatric gliomas, including glioblastoma (GBM) and diffuse midline glioma (DMG), using single-cell profiling and multi-omics technologies have revealed extensive tumor intrinsic and extrinsic heterogeneity, with phenotypically and genetically plastic tumor cells actively engaged with neurons, glia, vasculature, and immune compartments that collectively reshape the neural microenvironment to promote tumor growth, invasion, and therapy resistance. Conventional two-dimensional culture systems and animal models incompletely recapitulate these interactions, limiting mechanistic insights and constraining clinical translation to human patients. Recent advances in organoid technologies have addressed this gap, enabling the development of three-dimensional human-specific models of glioma-microenvironment interactions. Platforms such as iPSC-derived cerebral organoids, regionally patterned neural organoids, patient-derived glioma organoids and tumor-organoid co-culture systems capture essential features of these human diseases. These systems recapitulate tumor-neuron synaptic integration, diffuse invasion programs, activity-dependent tumor growth, hypoxia-structured niches, vascular interactions, and patient-specific therapeutic responses. In this review, we synthesize recent advances and biological insights gleaned across glioma organoid model systems and evaluate their strengths and limitations, including neurovascular and multi-lineage systems. We further highlight emerging innovations that enhance the physiological fidelity, reproducibility, and scalability of these models. Collectively, these platforms establish tumor microenvironment interactions as a central organizing principle of glioma biology and provide a strong foundation for mechanistic discovery, therapeutic development, and personalized neuro-oncology.
如何引用
AMA
Mohamed Ishan, Jorge Luis Jimenez-Macias, Renee D Read. Modeling gliomas with organoids: reconstructing the human neural microenvironment for translational neuro-oncology.. Frontiers in oncology. 2026; doi:10.3389/fonc.2026.1803705.
APA
Mohamed Ishan, Jorge Luis Jimenez-Macias, Renee D Read (2026). Modeling gliomas with organoids: reconstructing the human neural microenvironment for translational neuro-oncology.. Frontiers in oncology. https://doi.org/10.3389/fonc.2026.1803705
GB/T 7714
Mohamed Ishan, Jorge Luis Jimenez-Macias, Renee D Read. Modeling gliomas with organoids: reconstructing the human neural microenvironment for translational neuro-oncology.[J]. Frontiers in oncology, 2026 doi:10.3389/fonc.2026.1803705.
在 PubMed增强版 阅读全文
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出