Recent development of novel therapies has improved mobility and quality of life for people suffering from inheritable neuromuscular disorders. Despite this progress, the majority of neuromuscular disorders are still incurable, in part due to a lack of predictive models of neuromuscular junction (NMJ) breakdown. Improvement of predictive models of a human NMJ would be transformative in terms of expanding our understanding of the mechanisms that underpin development, maintenance, and disease, and as a testbed with which to evaluate novel therapeutics. Induced pluripotent stem cells (iPSCs) are emerging as a clinically relevant and non-invasive cell source to create human NMJs to study synaptic development and maturation, as well as disease modeling and drug discovery. This review will highlight the recent advances and remaining challenges to generating an NMJ capable of eliciting contraction of stem cell-derived skeletal muscle in vitro. We explore the advantages and shortcomings of traditional NMJ culturing platforms, as well as the pioneering technologies and novel, biomimetic culturing systems currently in use to guide development and maturation of the neuromuscular synapse and extracellular microenvironment. Then, we will explore how this NMJ-in-a-dish can be used to study normal assembly and function of the efferent portion of the neuromuscular arc, and how neuromuscular disease-causing mutations disrupt structure, signaling, and function.

中文翻译：

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在体外创建干细胞衍生的神经肌肉接头

新疗法的最新发展改善了患有遗传性神经肌肉疾病的人们的活动能力和生活质量。尽管取得了这一进展，但大多数神经肌肉疾病仍然无法治愈，部分原因是缺乏神经肌肉接头 (NMJ) 故障的预测模型。人类 NMJ 预测模型的改进将在扩大我们对支持发育、维持和疾病的机制的理解方面具有变革性，并作为评估新疗法的试验台。诱导多能干细胞 (iPSC) 正在成为一种临床相关的非侵入性细胞来源，用于创建人类 NMJ 以研究突触发育和成熟，以及疾病建模和药物发现。这篇综述将重点介绍在体外产生能够引起干细胞衍生骨骼肌收缩的 NMJ 的最新进展和仍然存在的挑战。我们探讨了传统 NMJ 培养平台的优缺点，以及目前用于指导神经肌肉突触和细胞外微环境的发育和成熟的开创性技术和新颖的仿生培养系统。然后，我们将探讨如何使用这种 NMJ-in-a-dish 来研究神经肌肉弧传出部分的正常组装和功能，以及神经肌肉疾病引起的突变如何破坏结构、信号传导和功能。我们探讨了传统 NMJ 培养平台的优缺点，以及目前用于指导神经肌肉突触和细胞外微环境的发育和成熟的开创性技术和新颖的仿生培养系统。然后，我们将探讨如何使用这种 NMJ-in-a-dish 来研究神经肌肉弧传出部分的正常组装和功能，以及神经肌肉疾病引起的突变如何破坏结构、信号传导和功能。我们探讨了传统 NMJ 培养平台的优缺点，以及目前用于指导神经肌肉突触和细胞外微环境的发育和成熟的开创性技术和新颖的仿生培养系统。然后，我们将探讨如何使用这种 NMJ-in-a-dish 来研究神经肌肉弧传出部分的正常组装和功能，以及神经肌肉疾病引起的突变如何破坏结构、信号传导和功能。