Current Progress in the Creation, Characterization, and Application of Human Stem Cell-derived in Vitro Neuromuscular...

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.