Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, and with the School of Engineering Medicine, Beihang University, Beijing, 100083, China.
State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, 100094, China.
Adv Mater. 2023 Oct;35(41):e2211059. doi: 10.1002/adma.202211059. Epub 2023 Jul 30.
The neuromuscular junction (NMJ) is a peripheral synaptic connection between presynaptic motor neurons and postsynaptic skeletal muscle fibers that enables muscle contraction and voluntary motor movement. Many traumatic, neurodegenerative, and neuroimmunological diseases are classically believed to mainly affect either the neuronal or the muscle side of the NMJ, and treatment options are lacking. Recent advances in novel techniques have helped develop in vitro physiological and pathophysiological models of the NMJ as well as enable precise control and evaluation of its functions. This paper reviews the recent developments in in vitro NMJ models with 2D or 3D cultures, from organ-on-a-chip and organoids to biohybrid robotics. Related derivative techniques are introduced for functional analysis of the NMJ, such as the patch-clamp technique, microelectrode arrays, calcium imaging, and stimulus methods, particularly optogenetic-mediated light stimulation, microelectrode-mediated electrical stimulation, and biochemical stimulation. Finally, the applications of the in vitro NMJ models as disease models or for drug screening related to suitable neuromuscular diseases are summarized and their future development trends and challenges are discussed.
神经肌肉接头（NMJ）是位于前运动神经元和后突触骨骼肌纤维之间的外周突触连接，使肌肉收缩和进行随意运动成为可能。许多创伤性、神经退行性和神经免疫性疾病通常被认为主要影响 NMJ 的神经元或肌肉侧，且缺乏治疗选择。新型技术的最新进展有助于开发 NMJ 的体外生理和病理生理模型，并能够精确控制和评估其功能。本文综述了 2D 或 3D 培养的 NMJ 体外模型的最新进展，包括器官芯片和类器官到生物混合机器人。介绍了相关的衍生技术，用于 NMJ 的功能分析，如膜片钳技术、微电极阵列、钙成像和刺激方法，特别是光遗传学介导的光刺激、微电极介导的电刺激和生化刺激。最后，总结了 NMJ 体外模型作为与合适的神经肌肉疾病相关的疾病模型或药物筛选的应用，并讨论了它们的未来发展趋势和挑战。
