Stem Cell Reviews and Reports ( IF 4.5 ) Pub Date : 2021-07-01 , DOI: 10.1007/s12015-021-10201-2 Eileen Lynch 1 , Emma Peek 1 , Megan Reilly 1 , Claire FitzGibbons 1 , Samantha Robertson 1 , Masatoshi Suzuki 1, 2
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Human pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) are of great value for studying developmental processes, disease modeling, and drug testing. One area in which the use of human PSCs has become of great interest in recent years is for in vitro models of the neuromuscular junction (NMJ). The NMJ is a synapse at which a motor neuron releases acetylcholine to bind to skeletal muscle and stimulate contraction. Degeneration of the NMJ and subsequent loss of muscle function is a common feature of many neuromuscular diseases such as myasthenia gravis, spinal muscular atrophy, and amyotrophic lateral sclerosis. In order to develop new therapies for patients with neuromuscular diseases, it is essential to understand mechanisms taking place at the NMJ. However, we have limited ability to study the NMJ in living human patients, and animal models are limited by physiological relevance. Therefore, an in vitro model of the NMJ consisting of human cells is of great value. The use of stem cells for in vitro NMJ models is still in progress and requires further optimization in order to yield reliable, reproducible results. The objective of this review is (1) to outline the current progress towards fully PSC-derived in vitro co-culture models of the human NMJ and (2) to discuss future directions and challenges that must be overcome in order to create reproducible fully PSC-derived models that can be used for developmental studies, disease modeling, and drug testing.
Graphical abstract
中文翻译：
人类干细胞体外神经肌肉接头模型的创建、表征和应用的当前进展
人类多能干细胞 (PSC)，例如胚胎干细胞 (ESC) 或诱导多能干细胞 (iPSC)，对于研究发育过程、疾病建模和药物测试具有重要价值。近年来，人类 PSC 的使用引起极大兴趣的一个领域是体外神经肌肉接头 (NMJ) 模型。NMJ 是一个突触，运动神经元在该突触处释放乙酰胆碱以与骨骼肌结合并刺激收缩。NMJ 退化和随后的肌肉功能丧失是许多神经肌肉疾病的共同特征，例如重症肌无力、脊髓性肌萎缩和肌萎缩侧索硬化。为了为神经肌肉疾病患者开发新疗法，了解 NMJ 发生的机制至关重要。然而，我们在活的人类患者中研究 NMJ 的能力有限，动物模型受到生理相关性的限制。因此，由人体细胞组成的 NMJ体外模型具有重要价值。干细胞在体外的应用NMJ 模型仍在进行中，需要进一步优化才能产生可靠、可重复的结果。本综述的目的是 (1) 概述人类 NMJ 完全 PSC 衍生的体外共培养模型的当前进展和 (2) 讨论为创建可重复的完全 PSC 必须克服的未来方向和挑战- 可用于发育研究、疾病建模和药物测试的衍生模型。
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