Neuromuscular Junction Modeling with iPSC-derived Motor Neurons and Skeletal Muscles


2020 ISSCR Poster Presentation

Co-culture of Human iPSC-derived Motor Neurons and Skeletal Muscles Provides a Physiological Neuromuscular Junction Model in-a-dish

Abstract: The Neuromuscular junction (NMJ) is a highly organized synapse which is formed between the axon of a motor neuron and a muscle fiber. Motor neurons transmit efferent signals to control the muscle fiber contraction.  The functional integrity of NMJ is tightly associated with the etiology, pathophysiology, and progression of neuromuscular diseases.  NMJ models have been well established using rodent cells, however, there is still a need to establish a human model due to the physiological differences between mouse and humans.  Here, we have established an NMJ model by co-culturing human motor neurons and skeletal muscles differentiated from the same human iPSC line.  The formation of functional NMJ connections are confirmed by imaging for muscle fiber calcium transients and the contractions in response to glutamate-induced motor neuron firing.  In the future, the application of this model using patient-derived iPSC cells as well as high throughput small molecule screen assay will deepen our research on the etiology and provide targeting molecule candidates that can improve the physiological function of NMJ.



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