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Review
. 2023 Oct 18;24(20):15291.
doi: 10.3390/ijms242015291.

Unlocking the Complexity of Neuromuscular Diseases: Insights from Human Pluripotent Stem Cell-Derived Neuromuscular Junctions

Morgan Gazzola  1 , Cécile Martinat  1
Affiliations
Review

Unlocking the Complexity of Neuromuscular Diseases: Insights from Human Pluripotent Stem Cell-Derived Neuromuscular Junctions

Morgan Gazzola et al. Int J Mol Sci. .

Abstract

Over the past 20 years, the use of pluripotent stem cells to mimic the complexities of the human neuromuscular junction has received much attention. Deciphering the key mechanisms underlying the establishment and maturation of this complex synapse has been driven by the dual goals of addressing developmental questions and gaining insight into neuromuscular disorders. This review aims to summarise the evolution and sophistication of in vitro neuromuscular junction models developed from the first differentiation of human embryonic stem cells into motor neurons to recent neuromuscular organoids. We also discuss the potential offered by these models to decipher different neuromuscular diseases characterised by defects in the presynaptic compartment, the neuromuscular junction, and the postsynaptic compartment. Finally, we discuss the emerging field that considers the use of these techniques in drug screening assay and the challenges they will face in the future.

Keywords: human neuromuscular junction; in vitro models; microfluidics and organoids; pluripotent stem cells.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The different established NMJ models derived from pluripotent stem cell differentiation.
See this image and copyright information in PMC

References

    1. Deenen J.C.W., Horlings C.G.C., Verschuuren J.J.G.M., Verbeek A.L.M., Van Engelen B.G.M. The Epidemiology of Neuromuscular Disorders: A Comprehensive Overview of the Literature. J. Neuromuscul. Dis. 2015;2:73–85. doi: 10.3233/JND-140045. - DOI - PubMed
    1. Benarroch L., Bonne G., Rivier F., Hamroun D. The 2023 version of the gene table of neuromuscular disorders (nuclear genome) Neuromuscul. Disord. 2023;33:76–117. doi: 10.1016/j.nmd.2022.12.002. - DOI - PubMed
    1. Boehm I., Alhindi A., Leite A.S., Logie C., Gibbs A., Murray O., Farrukh R., Pirie R., Proudfoot C., Clutton R., et al. Comparative anatomy of the mammalian neuromuscular junction. J. Anat. 2020;237:827–836. doi: 10.1111/joa.13260. - DOI - PMC - PubMed
    1. Doncheva N.T., Palasca O., Yarani R., Litman T., Anthon C., Groenen M.A.M., Stadler P.F., Pociot F., Jensen L.J., Gorodkin J. Human pathways in animal models: Possibilities and limitations. Nucleic Acids Res. 2021;49:1859–1871. doi: 10.1093/nar/gkab012. - DOI - PMC - PubMed
    1. Hu X., Charles J.P., Akay T., Hutchinson J.R., Blemker S.S. Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans. Skelet. Muscle. 2017;7:26. doi: 10.1186/s13395-017-0143-9. - DOI - PMC - PubMed