微流控体外系统在神经疾病建模方面的进展。

Advances in microfluidic in vitro systems for neurological disease modeling.

机构信息

Radcliffe Department of Medicine, University of Oxford, Oxford, UK.

Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK.

出版信息

J Neurosci Res. 2021 May;99(5):1276-1307. doi: 10.1002/jnr.24794. Epub 2021 Feb 13.

Abstract

Neurological disorders are the leading cause of disability and the second largest cause of death worldwide. Despite significant research efforts, neurology remains one of the most failure-prone areas of drug development. The complexity of the human brain, boundaries to examining the brain directly in vivo, and the significant evolutionary gap between animal models and humans, all serve to hamper translational success. Recent advances in microfluidic in vitro models have provided new opportunities to study human cells with enhanced physiological relevance. The ability to precisely micro-engineer cell-scale architecture, tailoring form and function, has allowed for detailed dissection of cell biology using microphysiological systems (MPS) of varying complexities from single cell systems to "Organ-on-chip" models. Simplified neuronal networks have allowed for unique insights into neuronal transport and neurogenesis, while more complex 3D heterotypic cellular models such as neurovascular unit mimetics and "Organ-on-chip" systems have enabled new understanding of metabolic coupling and blood-brain barrier transport. These systems are now being developed beyond MPS toward disease specific micro-pathophysiological systems, moving from "Organ-on-chip" to "Disease-on-chip." This review gives an outline of current state of the art in microfluidic technologies for neurological disease research, discussing the challenges and limitations while highlighting the benefits and potential of integrating technologies. We provide examples of where such toolsets have enabled novel insights and how these technologies may empower future investigation into neurological diseases.

摘要

神经紊乱是全球范围内导致残疾的首要原因和第二大致死原因。尽管进行了大量的研究工作,但神经科学仍然是药物开发中最容易失败的领域之一。人脑的复杂性、直接在体内研究大脑的局限性以及动物模型和人类之间显著的进化差距,都阻碍了转化的成功。最近微流控体外模型的进展为研究具有增强生理相关性的人类细胞提供了新的机会。精确微工程细胞尺度结构的能力,定制形态和功能,允许使用从单细胞系统到“器官芯片”模型的各种复杂程度的微生理系统(MPS)对细胞生物学进行详细剖析。简化的神经元网络使人们对神经元运输和神经发生有了独特的了解,而更复杂的 3D 异质细胞模型,如神经血管单元模拟物和“器官芯片”系统,使人们对代谢偶联和血脑屏障运输有了新的认识。这些系统现在正在从 MPS 向特定疾病的微病理生理系统发展,从“器官芯片”到“疾病芯片”。本文概述了用于神经疾病研究的微流控技术的最新现状,讨论了挑战和局限性,同时强调了整合技术的优势和潜力。我们提供了这些工具集如何使人们获得新的见解的示例,以及这些技术如何为未来对神经疾病的研究提供支持。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索