Chukwurah Evelyn, Osmundsen Allison, Davis Shannon W, Lizarraga Sofia B
Department of Biological Sciences, University of South Carolina, Columbia, SC, United States.
Center for Childhood Neurotherapeutics, University of South Carolina, Columbia, SC, United States.
Front Neurosci. 2019 Jun 21;13:582. doi: 10.3389/fnins.2019.00582. eCollection 2019.
The complex development of the human nervous system has been traditionally studied using a combination of animal models, human post-mortem brain tissue, and human genetics studies. However, there has been a lack of experimental human cellular models that would allow for a more precise elucidation of the intricate dynamics of early human brain development. The development of stem cell technologies, both embryonic and induced pluripotent stem cells (iPSCs), has given neuroscientists access to the previously inaccessible early stages of human brain development. In particular, the recent development of three-dimensional culturing methodologies provides a platform to study the differentiation of stem cells in both normal development and disease states in a more like context. Three-dimensional neural models or cerebral organoids possess an innate advantage over two-dimensional neural cultures as they can recapitulate tissue organization and cell type diversity that resemble the developing brain. Brain organoids also provide the exciting opportunity to model the integration of different brain regions . Furthermore, recent advances in the differentiation of non-neuronal tissue from stem cells provides the opportunity to study the interaction between the developing nervous system and other non-neuronal systems that impact neuronal function. In this review, we discuss the potential and limitations of the organoid system to study neurological diseases that arise in the neuroendocrine and the enteric nervous system or from interactions with the immune system.
传统上，人类神经系统的复杂发育是通过动物模型、人类尸检脑组织和人类遗传学研究相结合的方式进行研究的。然而，一直缺乏实验性的人类细胞模型，无法更精确地阐明人类早期大脑发育的复杂动态。干细胞技术的发展，包括胚胎干细胞和诱导多能干细胞（iPSC），使神经科学家能够接触到以前无法触及的人类大脑发育早期阶段。特别是，三维培养方法的最新发展提供了一个平台，以便在更接近真实的环境中研究干细胞在正常发育和疾病状态下的分化。三维神经模型或脑类器官相对于二维神经培养具有先天优势，因为它们可以重现类似于发育中大脑的组织结构和细胞类型多样性。脑类器官还为模拟不同脑区的整合提供了令人兴奋的机会。此外，干细胞分化为非神经组织的最新进展提供了机会，来研究发育中的神经系统与影响神经元功能的其他非神经系统之间的相互作用。在这篇综述中，我们讨论了类器官系统在研究神经内分泌和肠神经系统中出现的神经系统疾病或免疫系统相互作用引起的神经系统疾病方面的潜力和局限性。
