Microphysiological Human Brain and Neural Systems-on-a-Chip: Potential Alternatives to Small Animal Models and Emerging Platforms for Drug Discovery and Personalized Medicine.
Microphysiological Human Brain and Neural Systems-on-a-Chip: Potential Alternatives to Small Animal Models and Emerging Platforms for Drug Discovery and Personalized Medicine.
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DOI：
10.1007/s12015-017-9738-0
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发表时间：
2017-06
影响因子：
4.8
通讯作者：
Johnson BN
中科院分区：
文献类型：
--
作者：
Haring AP;Sontheimer H;Johnson BN
与简化论建模方法相关的翻译挑战，以及与小动物测试相关的伦理问题和经济影响，推动了开发用于模拟人类神经疾病、障碍和损伤的微生理神经系统的需求。在这里，我们提供了一个芯片上的微生理神经系统(NSCs)的全面回顾，以模拟人类神经系统的高阶轨迹。突出神经疾病、紊乱和损伤对社会、经济和国家安全的影响，以确定关键的NSC应用空间。讨论了NSCs的分层设计和制造，区分了表面系统和体基系统。识别和综述了三大类神经干细胞：微流控神经干细胞、分隔化神经干细胞和水凝胶神经干细胞。重点介绍了正在出现的领域和未来的发展方向，包括3D打印在设计和制造下一代神经干细胞方面的应用，干细胞用于构建患者特有的神经干细胞，以及人类神经干细胞在“个性化神经学”中的应用。讨论了技术障碍和剩余的挑战。这篇综述介绍了NSC的最新设计方法、制造方法和性能能力。这项工作表明，神经干细胞似乎准备彻底改变人类神经疾病、障碍和损伤的建模。
Translational challenges associated with reductionist modeling approaches, as well as ethical concerns and economic implications associated with small animal testing, drive the need for developing microphysiological neural systems for modeling human neurological diseases, disorders and injuries. Here, we provide a comprehensive review of microphysiological neural systems on a chip (NSCs) for modeling higher order trajectories in the human nervous system. Societal, economic, and national security impacts of neurological diseases, disorders and injuries are highlighted to identify critical NSC application spaces. Hierarchical design and manufacturing of NSCs are discussed with distinction of surface- and bulk-based systems. Three broad NSC classes are identified and reviewed: microfluidic NSCs, compartmentalized NSCs, and hydrogel NSCs. Emerging areas and future directions are highlighted, including the application of 3D printing to design and manufacturing of next-generation NSCs, the use of stem cells for constructing patient-specific NSCs, and the application of human NSCs to ‘personalized neurology’. Technical hurdles and remaining challenges are discussed. This review identifies the state-of-the-art design methodologies, manufacturing approaches, and performance capabilities of NSCs. This work suggests NSCs appear poised to revolutionize the modeling of human neurological diseases, disorders and injuries.
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DOI：
10.1038/nrd4539
发表时间：
2015-04
期刊：
Nature reviews. Drug discovery
影响因子：
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