Generation of Human Motor Units with Functional Neuromuscular Junctions in Microfluidic Devices

作者： Katarina Stoklund Dittlau1,2, Emily N. Krasnow1,2, Laura Fumagalli1,2, Tijs Vandoorne1,2, Pieter Baatsen3,4, Axelle Kerstens3,4, Giorgia Giacomazzi5, Benjamin Pavie3,4, Elisabeth Rossaert1,2, Jimmy Beckers1,2, Maurilio Sampaolesi5, Philip Van Damme1,2,6, Ludo Van Den Bosch1,2 1Department of Neurosciences, Experimental Neurology, and Leuven Brain Institute,KU Leuven - University of Leuven, 2VIB Bio Imaging Core,KU Leuven - University of Leuven, 3Department of Development and Regeneration, Stem Cell and Developmental Biology,KU Leuven - University of Leuven, 4Department of Neurology,University Hospitals Leuven

简介：

Overview

This study outlines a method for generating human motor units using commercially available microfluidic devices. By co-culturing human induced pluripotent stem cell-derived motor neurons with primary mesoangioblast-derived myotubes, functionally active neuromuscular junctions are formed. This model can be employed to investigate motor neuron disorders, particularly amyotrophic lateral sclerosis.

Key Study Components

Area of Science

• Neuroscience
• Stem Cell Biology
• Neuromuscular Junction Research

Background

• There is a need for models to study motor neuron disconnection and related diseases.
• The method utilizes standard stem cell technology.
• Microfluidic devices enhance reproducibility in experiments.
• Investigating such models can provide insights into strategies for combating neuromuscular disorders.

Purpose of Study

• Develop a humanized model for studying motor neuron disorders.
• Facilitate research on health and disease related to motor neurons and neuromuscular junctions.
• Provide a platform for understanding the early events in neuromuscular diseases.

Methods Used

• Microfluidic devices were employed as the primary experimental platform.
• The biological model consists of neuronal progenitor cells and myotubes.
• Key steps include sterilization, coating with Poly-L-ornithine and laminin, and cell seeding.
• The incubation periods and specific concentrations for the various reagents were meticulously established.

Main Results

• The development of active neuromuscular junctions was confirmed through the established model.
• It allows for the observation of cellular interactions essential for understanding motor neuron function.
• Results highlight potential avenues for therapeutic strategies in neuromuscular disease models.

Conclusions

• This study demonstrates a reliable method for modeling human motor units.
• It has significant implications for understanding neuronal mechanisms in health and disease.
• The findings emphasize the model's utility in developing treatments for neuromuscular disorders.

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