Abstract:

The brain, as the epicenter of human intelligence, sensation, and motor coordination, represents the pinnacle of biological complexity. Despite its critical role, the availability of live human brain tissue for research is fraught with challenges, impeding advancements in our understanding of the nervous system. Brain organoids are sophisticated three-dimensional cultures derived from human pluripotent stem cells that emulate the diverse cellular composition, structural intricacies, and functional attributes of the human brain. These organoids eclipse traditional two-dimensional cultures and animal models in mirroring the brain’s spatial organization and cellular interplay, bolstered by a genetic congruence with their human counterparts. This congruence renders them particularly adept at modeling neuropsychiatric conditions and pioneering cell-based therapeutic interventions. Regenerative medicine, a confluence of engineering and biological sciences, endeavors to restore tissues and organs compromised by aging, disease, or trauma. However, the field grapples with limitations stemming from the scarcity of samples and ethical quandaries. Brain organoid technology emerges as a formidable asset in this domain, offering expansive potential and profound implications for scientific inquiry. Recent strides have seen the successful assembly of organoid models representing various brain regions through the application of tissue engineering and directed differentiation. These models hold promise for simulating neuropathological states and facilitating tissue repair. This article meticulously surveys the cutting-edge methodologies for constructing organoids specific to brain regions such as the cerebral cortex, hippocampus, striatum, midbrain, thalamus, hypothalamus, cerebellum, and retina. It delineates the principal applications of brain organoids in regenerative medicine, encompassing injury simulation, exploration of inter-regional and multi-lineage cellular dynamics, drug efficacy and toxicity assessments, and the potential for organoid transplantation. Furthermore, the review addresses the prevailing obstacles in the application of brain organoids, notably their pronounced variability, absence of vascularization, and developmental immaturity. In essence, this review seeks to illuminate the organoid generation techniques tailored to discrete brain territories and their significance in regenerative medicine’s landscape. By probing into research poised to surmount the limitations of current models, it aspires to broaden the horizons for brain organoids in both foundational research and clinical applications.

Key words: brain organoids, drug screening, disease model, personalized medicine, regenerative medicine

摘要：

脑类器官是一种基于人多能干细胞的三维体外模型，能够模拟人脑的细胞异质性、结构和功能。再生医学是一个多学科交叉的领域，致力于应用工程学和生物学手段修复因年龄、疾病或外伤而受损的组织或器官。脑类器官技术作为再生医学领域的一种重要手段，具有广阔的应用前景和重要的科学意义。近年来，利用组织工程和诱导因子分化技术，研究人员成功构建出不同脑区的脑类器官模型，可用于模拟脑损伤或修复病变组织。本文将系统介绍包括大脑皮层、海马、纹状体、中脑、丘脑及下丘脑、小脑和视网膜在内的脑区特异类器官构建技术的最新进展，总结其在再生医学领域中的应用，并概括当前脑类器官应用面临的挑战，如异质性大、缺乏脉管系统和成熟度较低等。这将加深对人类大脑的理解，并增强脑类器官在基础研究和临床研究中的进一步应用。

关键词: 脑类器官, 药物筛选, 疾病模型, 个体化医疗, 再生医学