ArticleScientific reports2021
Bioengineered model of the human motor unit with physiologically functional neuromuscular junctions.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Using human 3D organoid models to gain mechanistic insight in motor neuron diseases.Nature reviews. Neuroscience · 2026Review
- Skeletal muscle reprogramming in peripheral nerve injury: mechanisms, therapeutic roles, and complication management.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- Electrophysiological characterization of sourced human iPSC-derived motor neurons.Channels (Austin, Tex.) · 2025Article
- Insights into human muscle biology from human primary skeletal muscle cell culture.Journal of muscle research and cell motility · 2025Review
- Development and modeling of cardiac autonomic innervation.Nature cardiovascular research · 2025Review
- Biohybrid motor neuron spheroid composed of graphene/HUVEC/neural cell for 3D biosensing system to evaluate drug of amyotrophic lateral sclerosis.Nano convergence · 2025Article
- Human iPSC-Derived Motor Neuron Innervation Enhances the Differentiation of Muscle Bundles Engineered with Benchtop Fabrication Techniques.ACS biomaterials science & engineering · 2025Article
- An automated platform for simultaneous, longitudinal analysis of engineered neuromuscular tissues for applications in neurotoxin potency testing.Current research in toxicology · 2025Article
- Human iPSC-derived motor neuron innervation enhances the differentiation of muscle bundles engineered with benchtop fabrication techniques.bioRxiv : the preprint server for biology · 2024Article
- Co-culture of postnatal mouse spinal cord and skeletal muscle explants as an experimental model of neuromuscular interactions.Histochemistry and cell biology · 2024Article
- Engineered myovascular tissues for studies of endothelial/satellite cell interactions.Acta biomaterialia · 2024Article
- Extracellular vesicles may provide an alternative detoxification pathway during skeletal muscle myoblast ageing.Journal of extracellular biology · 2024Article
- Disruption of Neuromuscular Junction Following Spinal Cord Injury and Motor Neuron Diseases.International journal of molecular sciences · 2024Review
- Advancements in 2D and 3D In Vitro Models for Studying Neuromuscular Diseases.International journal of molecular sciences · 2023Review
- Spinal Cord Organoids to Study Motor Neuron Development and Disease.Life (Basel, Switzerland) · 2023Review
- Functional bioengineered models of the central nervous system.Nature reviews bioengineering · 2023Review
- Optimization of Application-Driven Development ofTissue engineering. Part B, Reviews · 2022Review
- Review
- hiPSC-Derived Schwann Cells Influence Myogenic Differentiation in Neuromuscular Cocultures.Cells · 2021Article
- Organ-on-a-chip technologies to study neuromuscular disorders: possibilities, limitations, and future hopes.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Investigations of the human neuromuscular junction (NMJ) have predominately utilised experimental animals, model organisms, or monolayer cell cultures that fail to represent the physiological complexity of the synapse. Consequently, there remains a paucity of data regarding the development of the human NMJ and a lack of systems that enable investigation of the motor unit. This work addresses this need, providing the methodologies to bioengineer 3D models of the human motor unit. Spheroid culture of iPSC derived motor neuron progenitors augmented the transcription of OLIG2, ISLET1 and SMI32 motor neuron mRNAs ~ 400, ~ 150 and ~ 200-fold respectively compared to monolayer equivalents. Axon projections of adhered spheroids exceeded 1000 μm in monolayer, with transcription of SMI32 and VACHT mRNAs further enhanced by addition to 3D extracellular matrices in a type I collagen concentration dependent manner. Bioengineered skeletal muscles produced functional tetanic and twitch profiles, demonstrated increased acetylcholine receptor (AChR) clustering and transcription of MUSK and LRP4 mRNAs, indicating enhanced organisation of the post-synaptic membrane. The number of motor neuron spheroids, or motor pool, required to functionally innervate 3D muscle tissues was then determined, generating functional human NMJs that evidence pre- and post-synaptic membrane and motor nerve axon co-localisation. Spontaneous firing was significantly elevated in 3D motor units, confirmed to be driven by the motor nerve via antagonistic inhibition of the AChR. Functional analysis outlined decreased time to peak twitch and half relaxation times, indicating enhanced physiology of excitation contraction coupling in innervated motor units. Our findings provide the methods to maximise the maturity of both iPSC motor neurons and primary human skeletal muscle, utilising cell type specific extracellular matrices and developmental timelines to bioengineer the human motor unit for the study of neuromuscular junction physiology.
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