In vitro models of neuromuscular junctions and their potential for novel drug discovery and development

ABSTRACT

Introduction: Neuromuscular Junctions (NMJs) are the synapses between motor neurons and skeletal muscle fibers, and they are responsible for voluntary motor function. NMJs are affected at early stages of numerous neurodegenerative and neuroimmunological diseases. Due to the difficulty of systematically studying and manipulating NMJs in live subjects, in vitro systems with human tissue models would provide a powerful complement to simple cell cultures and animal models for mechanistic and drug development studies.

Areas covered: The authors review the latest advances in in vitro models of NMJs, from traditional cell co-culture systems to novel tissue culture approaches, with focus on disease modeling and drug testing.

Expert opinion: In recent years, more sophisticated in vitro models of human NMJs have been established. The combination of human stem cell technology with advanced tissue culture systems has resulted in systems that better recapitulate the human NMJ structure and function, and thereby allow for high-throughput quantitative functional measurements under both healthy and diseased conditions. Although they still have limitations, these advanced systems are increasingly demonstrating their utility for evaluating new therapies for motoneuron and autoimmune neuromuscular diseases, and we expect them to become an integral part of the drug discovery process in the near future.

KEYWORDS:

• Neuromuscular junction
• human stem cells
• bioengineering
• drug testing

Article highlights

• Neuromuscular junctions are affected in several neurodegenerative and neuroimmunological diseases for which there are currently very few treatment options.

• In vitro models allow for systematic manipulation and testing of human systems.

• Recent advances in stem cell technology, fabrication and tissue engineering have allowed for the development of in vitro NMJ models that recapitulate human physiology.

• Incorporation of novel techniques such as optogenetics and automated optical stimulation and sensing allows for precise control and evaluation of NMJ function.

• These models can be derived from patient cells for personalize medicine and human disease modeling.

• The combination of all these advances will allow for the generation of high-throughput systems for novel drug screening and development.

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Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors gratefully acknowledge the funding support of the National Institutes of Health (grants EB025765 and EB027062 to G Vunjak-Novakovic), New York State Department of Health (NYSTEM) (grant C32606GG to G Vunjak-Novakovic) and the Department of Defense (grant PR171955 to OF Vila).