Development of “organ-on-a-chip” systems for neuroscience applications are lagging due in part to the structural complexity of the nervous system and limited access of human neuronal & glial cells. In addition, rates for animal models in translating to human success are significantly lower for neurodegenerative diseases. Thus, a preclinical in vitro human cell-based model capable of providing critical clinical metrics such as nerve conduction velocity and histomorphometry are necessary to improve prediction and translation of in vitro data to successful clinical trials. To answer this challenge, we present an in vitro biomimetic model of all-human peripheral nerve tissue capable of showing robust neurite outgrowth (~5 mm), myelination of hNs by primary human Schwann cells (~5%), and evaluation of nerve conduction velocity (0.13–0.28 m/sec), previously unrealized for any human cell-based in vitro system. To the best of our knowledge, this Human Nerve-on-a-chip (HNoaC) system is the first biomimetic microphysiological system of myelinated human peripheral nerve which can be used for evaluating electrophysiological and histological metrics, the gold-standard assessment techniques previously only possible with in vivo studies.
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机译：用于神经科学应用的“芯片上器官”系统的开发滞后，部分原因是神经系统的结构复杂以及人类神经元和神经胶质细胞的访问受限。另外，对于神经退行性疾病，动物模型转化为人类成功的比率大大降低。因此，必须提供能够提供关键临床指标（例如神经传导速度和组织形态测量）的临床前体外人细胞模型，以改善体外数据对成功的临床试验的预测和转化。为了应对这一挑战，我们提出了一种全人类外周神经组织的体外仿生模型，该模型能够显示强大的神经突向外生长（〜5 mm），原代人雪旺氏细胞对hNs的髓鞘形成（〜5％）以及神经传导评估速度（0.13-0.28 m / sec），以前对于任何基于人类细胞的体外系统都无法实现。据我们所知，此人类片上神经（HNoaC）系统是第一个可模拟人外周神经有髓神经的仿生微生理系统，可用于评估电生理和组织学指标，以前仅是金标准评估技术体内研究可能。
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