Creating stem cell-derived neuromuscular junctions in vitro.

Autor: Luttrell SM; Department of Rehabilitation Medicine, University of Washington, Seattle, Washington, USA.; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington, USA., Smith AST; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington, USA.; Department of Physiology and Biophysics, University of Washington, Seattle, Washington, USA., Mack DL; Department of Rehabilitation Medicine, University of Washington, Seattle, Washington, USA.; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington, USA.; Department of Physiology and Biophysics, University of Washington, Seattle, Washington, USA.
Jazyk: angličtina
Zdroj: Muscle & nerve [Muscle Nerve] 2021 Oct; Vol. 64 (4), pp. 388-403. Date of Electronic Publication: 2021 Jul 30.
DOI: 10.1002/mus.27360
Abstrakt: Recent development of novel therapies has improved mobility and quality of life for people suffering from inheritable neuromuscular disorders. Despite this progress, the majority of neuromuscular disorders are still incurable, in part due to a lack of predictive models of neuromuscular junction (NMJ) breakdown. Improvement of predictive models of a human NMJ would be transformative in terms of expanding our understanding of the mechanisms that underpin development, maintenance, and disease, and as a testbed with which to evaluate novel therapeutics. Induced pluripotent stem cells (iPSCs) are emerging as a clinically relevant and non-invasive cell source to create human NMJs to study synaptic development and maturation, as well as disease modeling and drug discovery. This review will highlight the recent advances and remaining challenges to generating an NMJ capable of eliciting contraction of stem cell-derived skeletal muscle in vitro. We explore the advantages and shortcomings of traditional NMJ culturing platforms, as well as the pioneering technologies and novel, biomimetic culturing systems currently in use to guide development and maturation of the neuromuscular synapse and extracellular microenvironment. Then, we will explore how this NMJ-in-a-dish can be used to study normal assembly and function of the efferent portion of the neuromuscular arc, and how neuromuscular disease-causing mutations disrupt structure, signaling, and function.
(© 2021 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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