Human stem cell model of neuromuscular junction affected by the autoimmune disorder myasthenia gravis
November 2015
Sloan-Kettering Institute for Cancer Research, New York, USA
Myasthenia gravis is an autoimmune disorder that selectively targets neuromuscular junctions. The potential application of pluripotent stem cell (PSC) - derived neurons in regenerative medicine and disease modelling ideally requires their integration into complex functional human networks or tissues. Yet, one of the most important properties of neurons, namely their ability to form functional synapses and transmit information to appropriate downstream targets, remains largely unexplored in human organoids and other PSC-based model systems. In the present study, the researchers aimed at establishing a neuromuscular model by in vitro co-culturing of human PSC derived into spinal motorneurons and human myoblast-derived skeletal muscle. The disease was modelled by incubating these co-cultures with autoantibodies from myasthenia gravis patients. The model was shown to be able to simulate muscle contraction under the control of the neurons. Further, the data showed a reversible reduction in the amplitude of muscle contractions when using the autoantibodies. In conclusion, this neuromuscular junction assay has a significant potential for modelling neuromuscular diseases and regeneration.
Functional connectivity under optogenetic control allows modeling of human neuromuscular disease
Lorenz Studer, Julius A. Steinbeck
Added on: 10-28-2021
[1] https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(15)00460-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1934590915004609%3Fshowall%3Dtrue[2] https://data.jrc.ec.europa.eu/dataset/700397b2-edd7-4ed6-86f7-fc1b164ed432
