A 3D disease and regeneration model of peripheral nervous system-on-a-chip.
A 3D disease and regeneration model of peripheral nervous system-on-a-chip.
复制标题
DOI：
10.1126/sciadv.abd9749
复制
发表时间：
2021-01
期刊：
影响因子：
13.6
通讯作者：
Jeon NL
中科院分区：
文献类型：
--
作者：
Hyung S;Lee SR;Kim J;Kim Y;Kim S;Kim HN;Jeon NL
3D PNS疾病芯片能够监测病理生理过程，包括脱髓鞘和髓鞘再生。脱髓鞘疾病涉及髓鞘的损失，并最终导致神经系统问题。不幸的是，确切的机制仍然未知，也没有有效的治疗方法。为了克服这些局限性，需要一个可靠的和生理相关的体外模型。在这里，我们提出了一个三维的周围神经系统（PNS）微流体平台，概括了髓鞘形成，脱髓鞘，和髓鞘再生使用原代雪旺细胞（SC）和运动神经元（MN）的全谱。该平台基于三个不同的设计因素，能够在体外实现可再现的水凝胶图案化和MN和SC的长期稳定共培养超过40天。此外，按需可拆卸基底允许深入的生物分析。我们证明了通过溶血磷脂酰胆碱模仿节段性脱髓鞘的可能性，并通过应用两种药物：苯扎托品或甲钴胺恢复髓鞘结构。这种3D PNS疾病芯片可以作为一个潜在的平台，用于了解脱髓鞘的病理生理学和筛选髓鞘再生药物。
A 3D PNS disease–on–a–chip enables the monitoring of pathophysiological processes, including demyelination and remyelination. 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.
登录
查看更多内容
影响因子：
25
作者：
Babetto E;Wong KM;Beirowski B
通讯作者：
Beirowski B
影响因子：
4.6
作者：
Liu, Chun;Oikonomopoulos, Angelos;Wu, Joseph C.
通讯作者：
Wu, Joseph C.
影响因子：
3
作者：
Haastert, K;Grosskreutz, J;Claus, P
通讯作者：
Claus, P
影响因子：
9
作者：
Lee, Seung-Ryeol;Hyung, Sujin;Jeon, Noo Li
通讯作者：
Jeon, Noo Li
DOI：
10.1126/science.1188302
发表时间：
2010-06-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Huh D;Matthews BD;Mammoto A;Montoya-Zavala M;Hsin HY;Ingber DE
通讯作者：
Ingber DE