Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, Italy.
Center for Life Nano- and Neuro-Science of Istituto Italiano di Tecnologia (IIT), 00161 Rome, Italy.
Int J Mol Sci. 2023 Jun 28;24(13):10762. doi: 10.3390/ijms241310762.
Understanding the complexities of the human brain and its associated disorders poses a significant challenge in neuroscience. Traditional research methods have limitations in replicating its intricacies, necessitating the development of in vitro models that can simulate its structure and function. Three-dimensional in vitro models, including organoids, cerebral organoids, bioprinted brain models, and functionalized brain organoids, offer promising platforms for studying human brain development, physiology, and disease. These models accurately replicate key aspects of human brain anatomy, gene expression, and cellular behavior, enabling drug discovery and toxicology studies while providing insights into human-specific phenomena not easily studied in animal models. The use of human-induced pluripotent stem cells has revolutionized the generation of 3D brain structures, with various techniques developed to generate specific brain regions. These advancements facilitate the study of brain structure development and function, overcoming previous limitations due to the scarcity of human brain samples. This technical review provides an overview of current 3D in vitro models of the human cortex, their development, characterization, and limitations, and explores the state of the art and future directions in the field, with a specific focus on their applications in studying neurodevelopmental and neurodegenerative disorders.
理解人类大脑及其相关疾病的复杂性是神经科学面临的重大挑战。传统的研究方法在复制其复杂性方面存在局限性，因此需要开发能够模拟其结构和功能的体外模型。三维体外模型，包括类器官、大脑类器官、生物打印脑模型和功能化脑类器官，为研究人类大脑发育、生理学和疾病提供了有前途的平台。这些模型准确地复制了人类大脑解剖、基因表达和细胞行为的关键方面，能够进行药物发现和毒理学研究，同时提供了对动物模型不易研究的人类特有的现象的深入了解。人类诱导多能干细胞的使用彻底改变了三维脑结构的生成，已经开发出各种技术来生成特定的脑区。这些进展促进了脑结构发育和功能的研究，克服了由于人类大脑样本稀缺而导致的先前限制。本技术综述概述了当前人类大脑皮层的三维体外模型及其发展、特性和局限性，并探讨了该领域的最新技术和未来方向，特别关注它们在研究神经发育和神经退行性疾病中的应用。
