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体外模拟神经肌肉接头:研究神经肌肉接头疾病的一种方法。

Modeling the neuromuscular junction in vitro: an approach to study neuromuscular junction disorders.

机构信息

Instituto de Fisiología Celular-Neurociencias, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico.

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montréal, Quebec, Canada.

出版信息

Ann N Y Acad Sci. 2021 Mar;1488(1):3-15. doi: 10.1111/nyas.14504. Epub 2020 Oct 10.

DOI:10.1111/nyas.14504
PMID:33040338
Abstract

The neuromuscular junction (NMJ) is a specialized structure that works as an interface to translate the action potential of the presynaptic motor neuron (MN) in the contraction of the postsynaptic myofiber. The design of appropriate experimental models is essential to have efficient and reliable approaches to study NMJ development and function, but also to generate conditions that recapitulate distinct features of diseases. Initial studies relied on the use of tissue slices maintained under the same environment and in which single motor axons were difficult to trace. Later, MNs and muscle cells were obtained from primary cultures or differentiation of progenitors and cocultured as monolayers; however, the tissue architecture was lost. Current approaches include self-assembling 3D structures or the incorporation of biomaterials with cells to generate engineered tissues, although the incorporation of Schwann cells remains a challenge. Thus, numerous investigations have established different NMJ models, some of which are quite complex and challenging. Our review summarizes the in vitro models that have emerged in recent years to coculture MNs and skeletal muscle, trying to mimic the healthy and diseased NMJ. We expect our review may serve as a reference for choosing the appropriate experimental model for the required purposes of investigation.

摘要

神经肌肉接头(NMJ)是一种特殊的结构,作为一种界面,将前突触运动神经元(MN)的动作电位转化为后突触肌纤维的收缩。设计合适的实验模型对于研究 NMJ 的发育和功能,以及产生能够重现疾病不同特征的条件至关重要。最初的研究依赖于使用在相同环境下维持的组织切片,其中单个运动轴突很难追踪。后来,MNs 和肌肉细胞从原代培养或祖细胞分化中获得,并作为单层共培养;然而,组织架构丢失了。目前的方法包括自组装 3D 结构或用细胞掺入生物材料来生成工程组织,尽管 Schwann 细胞的掺入仍然是一个挑战。因此,许多研究已经建立了不同的 NMJ 模型,其中一些模型非常复杂和具有挑战性。我们的综述总结了近年来出现的共培养 MN 和骨骼肌的体外模型,试图模拟健康和患病的 NMJ。我们希望我们的综述可以作为选择适当的实验模型的参考,以满足所需的研究目的。

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