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Updated: Nov 3, 2025
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Generation of Human Motor Units with Functional Neuromuscular Junctions in Microfluidic Devices
Published on: September 7, 2021
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Bioengineered model of the human motor unit with physiologically functional neuromuscular junctions
Rowan P Rimington1, Jacob W Fleming2, Andrew J Capel2
1National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, LE11 3TU, Leicestershire, UK. R.Rimington@lboro.ac.uk.
Scientific Reports
|June 4, 2021
Summary
Researchers developed 3D bioengineered models of the human motor unit, creating functional neuromuscular junctions (NMJs) for studying synapse development and motor unit physiology.
Area of Science:
- Biomedical Engineering
- Neuroscience
- Cell Biology
Background:
- Current models of the human neuromuscular junction (NMJ) lack physiological complexity, limiting research on human motor unit development.
- Existing systems fail to adequately represent the intricate structure and function of the human NMJ.
Purpose of the Study:
- To develop methodologies for bioengineering 3D models of the human motor unit.
- To create functional human neuromuscular junctions for studying synapse physiology.
Main Methods:
- Utilized induced pluripotent stem cell (iPSC)-derived motor neuron progenitors in spheroid cultures.
- Incorporated motor neurons and bioengineered skeletal muscle into 3D extracellular matrices.
- Determined optimal motor neuron numbers for functional innervation of muscle tissues.
Main Results:
- Spheroid cultures significantly enhanced motor neuron progenitor transcription.
- 3D extracellular matrices further boosted axon growth and specific mRNA transcription.
- Bioengineered muscles showed functional muscle profiles, enhanced acetylcholine receptor clustering, and improved NMJ organization.
- Successfully generated functional human NMJs with co-localized pre- and post-synaptic membranes and motor axons.
- Innervated 3D motor units exhibited elevated spontaneous firing and improved excitation-contraction coupling.
Conclusions:
- The developed methods enable the bioengineering of mature human motor units and NMJs.
- These 3D models provide a platform for studying human NMJ physiology.
- This approach advances the investigation of motor unit disorders and therapeutics.
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