Hyung Sujin, Lee Seung-Ryeol, Kim Jiho, Kim Youngtaek, Kim Suryong, Kim Hong Nam, Jeon Noo Li
Department of Mechanical Engineering, Seoul National University, Seoul, Republic of Korea.
Bio-MAX Institute, Seoul National University, Seoul, Republic of Korea.
Sci Adv. 2021 Jan 29;7(5). doi: 10.1126/sciadv.abd9749. Print 2021 Jan.
Demyelinating diseases involve loss of myelin sheaths and eventually lead to neurological problems. Unfortunately, the precise mechanisms remain unknown, and there are no effective therapies. To overcome these limitations, a reliable and physiologically relevant in vitro model is required. Here, we present a three-dimensional peripheral nervous system (PNS) microfluidic platform that recapitulates the full spectrum of myelination, demyelination, and remyelination using primary Schwann cells (SCs) and motor neurons (MNs). The platform enables reproducible hydrogel patterning and long-term stable coculture of MNs and SCs over 40 days in vitro based on three distinct design factors. Furthermore, the on-demand detachable substrate allows in-depth biological analysis. We demonstrated the possibility of mimicking segmental demyelination by lysophosphatidylcholine, and recovery of myelin structure by application of two drugs: benzatropine or methylcobalamin. This 3D PNS disease-on-a-chip may serve as a potential platform for understanding the pathophysiology of demyelination and screening drugs for remyelination.
脱髓鞘疾病涉及髓鞘的丧失，并最终导致神经问题。不幸的是，确切机制仍然未知，且没有有效的治疗方法。为了克服这些局限性，需要一个可靠且与生理相关的体外模型。在此，我们展示了一个三维外周神经系统（PNS）微流控平台，该平台利用原代雪旺细胞（SCs）和运动神经元（MNs）概括了髓鞘形成、脱髓鞘和髓鞘再生的全过程。基于三个不同的设计因素，该平台能够在体外实现可重复的水凝胶图案化以及MNs和SCs长达40天的长期稳定共培养。此外，按需可拆卸的底物允许进行深入的生物学分析。我们证明了通过溶血磷脂酰胆碱模拟节段性脱髓鞘以及应用两种药物（苯海索或甲钴胺）恢复髓鞘结构的可能性。这种3D PNS芯片上疾病模型可能成为理解脱髓鞘病理生理学和筛选髓鞘再生药物的潜在平台。
