ArticleFrontiers in cellular neuroscience2015
Generation of Functional Neuromuscular Junctions from Human Pluripotent Stem Cell Lines.
Article in Frontiers in cellular neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Efficient generation of a self-organizing neuromuscular junction model from human pluripotent stem cells.Nature communications · 2023Article
- Unlocking the Complexity of Neuromuscular Diseases: Insights from Human Pluripotent Stem Cell-Derived Neuromuscular Junctions.International journal of molecular sciences · 2023Review
- Efficient generation of lower induced motor neurons by coupling Ngn2 expression with developmental cues.Cell reports · 2023Article
- Optimization of Application-Driven Development ofTissue engineering. Part B, Reviews · 2022Review
- Human fetal membrane-mesenchymal stromal cells generate functional spinal motor neuronsiScience · 2022Article
- Current Progress in the Creation, Characterization, and Application of Human Stem Cell-derived in Vitro Neuromuscular Junction Models.Stem cell reviews and reports · 2022Review
- Human mesenchymal amniotic fluid stem cells reveal an unexpected neuronal potential differentiating into functional spinal motor neurons.Frontiers in cell and developmental biology · 2022Article
- Optogenetically controlled human functional motor endplate for testing botulinum neurotoxins.Stem cell research & therapy · 2021Article
- Human muscle production in vitro from pluripotent stem cells: Basic and clinical applications.Seminars in cell & developmental biology · 2021Review
- Creating stem cell-derived neuromuscular junctions in vitro.Muscle & nerve · 2021Review
- Human motor units in microfluidic devices are impaired by FUS mutations and improved by HDAC6 inhibition.Stem cell reports · 2021Article
- Cross-talk between motor neurons and myotubes via endogenously secreted neural and muscular growth factors.Physiological reports · 2021Article
- Tissue-Engineered Skeletal Muscle Models to Study Muscle Function, Plasticity, and Disease.Frontiers in physiology · 2021Review
- A Human-Based Functional NMJ System for Personalized ALS Modeling and Drug Testing.Advanced therapeutics · 2020Article
- Integrating CRISPR Engineering and hiPSC-Derived 2D Disease Modeling Systems.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Review
- hiPSC-Derived Neurons Provide a Robust and Physiologically RelevantFrontiers in pharmacology · 2020Article
- A customizable microfluidic platform for medium-throughput modeling of neuromuscular circuits.Biomaterials · 2019Article
- iPSC-derived functional human neuromuscular junctions model the pathophysiology of neuromuscular diseases.JCI insight · 2019Article
- One Step Into the Future: New iPSC Tools to Advance Research in Parkinson's Disease and Neurological Disorders.Journal of Parkinson's disease · 2019Review
- Stem cell derived phenotypic human neuromuscular junction model for dose response evaluation of therapeutics.Biomaterials · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several neuromuscular diseases involve dysfunction of neuromuscular junctions (NMJs), yet there are no patient-specific human models for electrophysiological characterization of NMJ. We seeded cells of neurally-induced embryoid body-like spheres derived from induced pluripotent stem cell (iPSC) or embryonic stem cell (ESC) lines as monolayers without basic fibroblast factor (bFGF) and observed differentiation of neuronal as well as spontaneously contracting, multinucleated skeletal myotubes. The myotubes showed striation, immunoreactivity for myosin heavy chain, actin bundles typical for myo-oriented cells, and generated spontaneous and evoked action potentials (APs). The myogenic differentiation was associated with expression of MyoD1, myogenin and type I ryanodine receptor. Neurons formed end plate like structures with strong binding of α-bungarotoxin, a marker of nicotinic acetylcholine receptors highly expressed in the postsynaptic membrane of NMJs, and expressed SMI-32, a motoneuron marker, as well as SV2, a marker for synapses. Pharmacological stimulation of cholinergic receptors resulted in strong depolarization of myotube membrane and raised Ca(2+) concentration in sarcoplasm, while electrical stimulation evoked Ca(2+) transients in myotubes. Stimulation of motoneurons with N-Methyl-D-aspartate resulted in reproducible APs in myotubes and end plates displayed typical mEPPs and tonic activity depolarizing myotubes of about 10 mV. We conclude that simultaneous differentiation of neurons and myotubes from patient-specific iPSCs or ESCs results also in the development of functional NMJs. Our human model of NMJ may serve as an important tool to investigate normal development, mechanisms of diseases and novel drug targets involving NMJ dysfunction and degeneration.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.