Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA.
Brain Res. 2020 Sep 1;1742:146803. doi: 10.1016/j.brainres.2020.146803. Epub 2020 Mar 30.
Rodent models have catalyzed major discoveries in the neocortex, a brain region unique to mammals. However, since the neocortex has expanded considerably in primates, employing rodent models has limitations. Human fetal brain tissue is a scarce resource with limitations for experimental manipulations. In order to create an experimentally tractable representation of human brain development, a number of labs have recently created in vitro models of the developing human brain. These models, generated using human embryonic stem cells or induced pluripotent stem cells, are called "organoids". Organoids have successfully and rapidly uncovered new mechanisms of human brain development in health and disease. In the future, we envision that this strategy will enable faster and more efficient translation of basic neuroscience findings to therapeutic applications. In this review, we discuss the generation of the first human cerebral organoids, progress since their debut, and challenges to be overcome in the future.
啮齿动物模型促进了大脑新皮层的重大发现,大脑新皮层是哺乳动物所特有的脑区。然而,由于灵长类动物的大脑新皮层有了显著的扩展,使用啮齿动物模型存在一定的局限性。人类胎儿脑组织是一种稀缺资源,其实验操作受到限制。为了创建一种可用于实验的人类大脑发育模型,最近有一些实验室已经创建了体外人类大脑发育模型。这些模型是用人胚胎干细胞或诱导多能干细胞生成的,被称为“类器官”。类器官在健康和疾病状态下成功且快速地揭示了人类大脑发育的新机制。在未来,我们设想这种策略将使基础神经科学研究成果更快、更有效地转化为治疗应用。在这篇综述中,我们讨论了第一代人类大脑类器官的产生、自问世以来的进展,以及未来需要克服的挑战。