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Generation of Human Motor Units with Functional Neuromuscular Junctions in Microfluidic Devices
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Human neuromuscular junction on micro-structured microfluidic devices implemented with a custom micro electrode array

Pauline Duc1, Michel Vignes2, Gérald Hugon3

  • 1IGMM, University of Montpellier, CNRS, Montpellier, France. pauline.duc@igmm.cnrs.fr.

Lab on a Chip
|September 24, 2021
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Summary

Researchers developed a novel microfluidic device to model human neuromuscular junctions (hNMJs) on-a-chip. This platform enables electrical stimulation of motor neurons and recording of muscle activity, offering a new tool for studying neurodegenerative diseases.

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Area of Science:

  • Neuroscience
  • Biomedical Engineering
  • Cell Biology

Background:

  • Signal transmission at the neuromuscular junction (NMJ) is vital for muscle function and health.
  • Understanding human NMJ (hNMJ) functionality requires advanced in vitro models.
  • Microfluidic platforms offer controlled environments for co-culturing different cell types.

Purpose of the Study:

  • To develop an on-a-chip device for modeling functional human neuromuscular junctions (hNMJs).
  • To create a platform enabling selective stimulation of motor neurons and recording of muscle activity.
  • To establish a physiologically relevant model for studying hNMJ function and neurodegenerative diseases.

Main Methods:

  • Integration of microfluidics, soft lithography, and custom microelectrode arrays (MEAs).
  • Micromachining to guide muscle fiber growth over electrodes for optimized recording.
  • Compartmentalization of motor neurons and muscle cells for selective manipulation.
  • Electrical stimulation of pre-synaptic axons and recording of post-synaptic muscle action potentials.

Main Results:

  • Successful creation of mature and functional in vitro hNMJs on the microelectrode array.
  • Demonstration of electrically evoked muscle action potentials upon motor neuron stimulation.
  • Validation of the platform's ability to isolate and assess NMJ functionality.

Conclusions:

  • The developed microfluidic/microstructured/MEA platform provides a robust model for in vitro hNMJ studies.
  • This model allows for precise electrical stimulation and recording, offering advantages over traditional methods like calcium imaging.
  • The platform serves as a powerful tool for investigating NMJ function and its disruption in neurodegenerative conditions.