Porciúncula Lisiane O, Goto-Silva Livia, Ledur Pitia F, Rehen Stevens K
Department of Biochemistry, Program of Biological Sciences - Biochemistry, Institute of Health and Basic Sciences, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.
Front Neurosci. 2021 Aug 13;15:674563. doi: 10.3389/fnins.2021.674563. eCollection 2021.
Over the past years, brain development has been investigated in rodent models, which were particularly relevant to establish the role of specific genes in this process. However, the cytoarchitectonic features, which determine neuronal network formation complexity, are unique to humans. This implies that the developmental program of the human brain and neurological disorders can only partly be reproduced in rodents. Advancement in the study of the human brain surged with cultures of human brain tissue in the lab, generated from induced pluripotent cells reprogrammed from human somatic tissue. These cultures, termed brain organoids, offer an invaluable model for the study of the human brain. Brain organoids reproduce the cytoarchitecture of the cortex and can develop multiple brain regions and cell types. Integration of functional activity of neural cells within brain organoids with genetic, cellular, and morphological data in a comprehensive model for human development and disease is key to advance in the field. Because the functional activity of neural cells within brain organoids relies on cell repertoire and time in culture, here, we review data supporting the gradual formation of complex neural networks in light of cell maturity within brain organoids. In this context, we discuss how the technology behind brain organoids brought advances in understanding neurodevelopmental, pathogen-induced, and neurodegenerative diseases.
在过去的几年里，人们在啮齿动物模型中对大脑发育进行了研究，这对于确定特定基因在这一过程中的作用尤为重要。然而，决定神经元网络形成复杂性的细胞结构特征是人类所特有的。这意味着人类大脑的发育程序和神经疾病只能在一定程度上在啮齿动物中重现。随着实验室中由人类体细胞重编程诱导多能细胞产生的人类脑组织培养物的出现，人类大脑研究取得了进展。这些培养物被称为脑类器官，为人类大脑研究提供了一个非常有价值的模型。脑类器官再现了皮质的细胞结构，并且可以发育出多个脑区和细胞类型。将脑类器官中神经细胞的功能活动与人类发育和疾病的综合模型中的遗传、细胞和形态学数据相结合，是该领域取得进展的关键。由于脑类器官中神经细胞的功能活动依赖于细胞组成和培养时间，在此，我们根据脑类器官内细胞的成熟情况，综述支持复杂神经网络逐渐形成的数据。在此背景下，我们讨论了脑类器官背后的技术如何在理解神经发育、病原体诱导和神经退行性疾病方面取得进展。
