Advances of organoids in the study of nervous system diseases: A narrative review

Traditional two-dimensional cellular models and patient-derived xenograft models have limitations in simulating human brain structure and function. In recent years, brain organoid technology has emerged as a novel three-dimensional tissue culture method, offering new avenues for studying neurological diseases. The purpose of this review is to overview the development of brain organoid technology with a focus on its applications in cerebrovascular diseases, brain tumors, and neurodegenerative disorders, as well as to discuss current challenges and future directions. Brain organoid technology enables more realistic reproduction of disease states by simulating the three-dimensional structure of the human brain. In cerebrovascular diseases, vascularized brain organoids offer a novel model for research, despite the existing limitations in vascularization. In brain tumor research, this technology can construct the models that closely resemble the tumor characteristics of patients, thereby uncovering the molecular mechanisms underlying tumorigenesis. In neurodegenerative diseases, brain organoid technology facilitates the exploration of disease pathology and potential therapeutic strategies. Compared with traditional models such as two-dimensional cell cultures, brain organoid technology provides a more physiologically relevant environment for studying complex cell-cell and cell-microenvironment interactions. In the field of cerebrovascular diseases, researchers have developed five methods for vascularizing brain organoids: co-culture with endothelial cells, co-culture with vascular organoids, organoid-on-a-chip technology, three-dimensional bioprinting of organoids, spontaneous vascularization of brain organoids, and the establishment of stroke organoid models. Various brain tumor organoid models, such as glioblastoma, medulloblastoma, and meningioma, have been successfully established. Similarly, organoid models for neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, have also been developed. Brain organoid technology offers a powerful tool for disease modeling in the field of neuroscience, enhancing our understanding of the mechanisms underlying neurological disorders and the development of novel therapeutic approaches.

摘要

传统二维细胞模型和患者来源的异种移植模型在模拟人类大脑结构和功能方面存在局限。近年来，脑类器官技术作为一种新兴的三维组织培养方法，为研究神经系统疾病提供了新的途径。此综述的目的是在概述脑类器官技术的发展，重点讨论其在脑血管疾病、脑肿瘤和神经退行性疾病中的应用，并探讨当前面临的挑战和未来的发展方向。脑类器官技术通过模拟人脑的三维结构，能够更真实地重现疾病状态。在脑血管疾病方面，血管化的脑类器官为研究提供了新的模型，尽管仍存在血管化不足的限制。在脑肿瘤研究方面，脑类器官技术能够构建出与患者肿瘤特征高度相似的模型，有助于揭示肿瘤发生的分子机制。在神经退行性疾病研究方面，脑类器官技术有助于探索疾病的病理进程和潜在治疗策略。与二维细胞培养等传统模型相比，类脑器官技术为研究复杂的细胞-细胞和细胞-微环境相互作用提供了更贴近生理的环境。在脑血管疾病领域，研究人员已开发出五种脑器官样体血管化方法：与内皮细胞共培养、与血管器官样体共培养、器官样体芯片技术、器官样体三维生物打印、脑器官样体自发血管化和建立脑卒中器官样体模型。目前已成功建立了多种脑肿瘤类器官模型，如胶质母细胞瘤、髓母细胞瘤和脑膜瘤。同样，针对神经退行性疾病（如阿尔茨海默病和帕金森病）的类器官模型也已建立。脑类器官技术为神经科学领域提供了一种强大的疾病建模工具，能够促进对神经系统疾病机制的理解和新型治疗方法的开发。