Modeling nervous system tumors with human stem cells and organoids.
Modeling nervous system tumors with human stem cells and organoids.
复制标题
用人类干细胞和类器官模拟神经系统肿瘤。
DOI：
10.1186/s13619-022-00150-7
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发表时间：
2023-03-01
影响因子：
--
通讯作者：
Wang, Yuan
中科院分区：
文献类型：
--
作者：
Duan, Jie;Wang, Yuan
关键词：
神经系统癌症是全球第十大死亡原因，其中许多癌症难以诊断，并表现出不同程度的治疗耐药性。现有的癌症模型，如患者来源的异种移植（PDX）模型和基因工程小鼠（GEM）模型的局限性，要求开发新的临床前癌症模型，以更忠实地模拟患者的癌症并提供额外的见解。人类干细胞生物学、类器官和基因组编辑技术的最新进展使我们能够在三种类型的下一代肿瘤模型中模拟神经系统肿瘤：细胞起源模型、肿瘤类器官和3D多细胞共培养模型。在这篇综述中，我们介绍和比较了不同的人类干细胞/类器官衍生的模型，并全面总结和讨论了最近发展的各种中枢和周围神经系统原发性肿瘤的模型，包括胶质母细胞瘤（GBM）、h3k27m突变的弥漫性中线胶质瘤（DMG）和h3g34r突变的高级别胶质瘤（HGG）、低级别胶质瘤（LGG）、1型神经纤维瘤病（NF1）、2型神经纤维瘤病（NF2）、成神经管细胞瘤（MB）、非典型畸胎瘤/横纹肌样瘤（AT/RT）和脑膜瘤。我们进一步将这些模型与PDX和GEM模型进行了比较，并讨论了利用人类干细胞和类器官进行神经肿瘤精确建模的机遇和挑战。
Nervous system cancers are the 10th leading cause of death worldwide, many of which are difficult to diagnose and exhibit varying degrees of treatment resistance. The limitations of existing cancer models, such as patient-derived xenograft (PDX) models and genetically engineered mouse (GEM) models, call for the development of novel preclinical cancer models to more faithfully mimic the patient’s cancer and offer additional insights. Recent advances in human stem cell biology, organoid, and genome-editing techniques allow us to model nervous system tumors in three types of next-generation tumor models: cell-of-origin models, tumor organoids, and 3D multicellular coculture models. In this review, we introduced and compared different human stem cell/organoid-derived models, and comprehensively summarized and discussed the recently developed models for various primary tumors in the central and peripheral nervous systems, including glioblastoma (GBM), H3K27M-mutant Diffuse Midline Glioma (DMG) and H3G34R-mutant High-grade Glioma (HGG), Low-grade Glioma (LGG), Neurofibromatosis Type 1 (NF1), Neurofibromatosis Type 2 (NF2), Medulloblastoma (MB), Atypical Teratoid/rhabdoid Tumor (AT/RT), and meningioma. We further compared these models with PDX and GEM models, and discussed the opportunities and challenges of precision nervous cancer modeling with human stem cells and organoids.
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