Ajongbolo Aderonke O, Langhans Sigrid A
Division of Neurology, Nemours Children's Health, Wilmington, DE 19803, USA.
Biological Sciences Graduate Program, University of Delaware, Newark, DE 19716, USA.
Cells. 2025 Jun 4;14(11):842. doi: 10.3390/cells14110842.
Brain organoids are self-organized, three-dimensional (3D) aggregates derived from human embryonic stem cells, induced pluripotent stem cells, or primary organs with cell types and cellular architectures resembling those of the developing human brain. Recent studies have shown the use of region-specific brain organoids for modeling various diseases ranging from neurodevelopmental and neurodegenerative diseases to different brain cancers, which have numerous applications in fundamental research and the development of new drugs, personalized treatment, and regenerative medicine. Consequently, the use of brain organoids in drug discovery is complex and challenging and still an emerging area in this field. This review article summarizes the primary stem cells used in brain organoid generation, region-specific brain organoids, and the functional assays used in their characterization. In addition, we discuss the use of brain organoids in modeling neurodevelopmental and neurodegenerative diseases and pediatric brain cancers, as well as the application of organoids, assembloids, and tumoroids in cancer neuroscience. We further explore the recent advances in using brain organoids in high-throughput screening to improve their use for drug discovery.
脑类器官是由人类胚胎干细胞、诱导多能干细胞或原代器官衍生而来的自组织三维（3D）聚集体，其细胞类型和细胞结构类似于发育中的人类大脑。最近的研究表明，使用区域特异性脑类器官可模拟从神经发育和神经退行性疾病到不同脑癌的各种疾病，这在基础研究以及新药开发、个性化治疗和再生医学中具有众多应用。因此，在药物发现中使用脑类器官既复杂又具有挑战性，并且仍然是该领域的一个新兴领域。这篇综述文章总结了用于生成脑类器官的主要干细胞、区域特异性脑类器官以及用于其表征的功能测定。此外，我们讨论了脑类器官在模拟神经发育和神经退行性疾病以及小儿脑癌方面的应用，以及类器官、组装体和肿瘤类器官在癌症神经科学中的应用。我们进一步探讨了在高通量筛选中使用脑类器官以改善其在药物发现中的应用的最新进展。
