3D muscle-nerve interactions on a Chip

iPSC-based NMJ-on-a-chip for neuromuscular disease modelling (NOACH, NMJ-On-A-CHip)

Untreatable neuromuscular disorders form an increasing burden in our ageing society. To facilitate research towards the cause and consequences as well as (novel) treatments for these disorders, a public-private partnership has been established between LUMC and PimBio. Together, they will develop a novel chip that allows for co-culture of nerves and muscles bundles in a 3D fashion. These experiments will make use of reprogrammed human cells which allows for neuromuscular disease modelling in a human genetic context. This will yield more insight on human disease mechanisms, increase the likelihood of translating research findings into actual treatments for patients and spare experimental animals.    

In The Netherlands ~200,000 patients suffer from a neuromuscular disease. Approximately 600 neuromuscular diseases are known to date. These disorders are often very debilitating as they affect the use of muscle and thereby daily life activities like walking, breathing and communication. This hampers the participation in societal activities and reduces the capacity for patients to work. Despite the impact and severity of these disorders, for only a few treatment is available.  

Current nerve-muscle models have been critical in unravelling healthy and diseased nerve-muscle interactions, but they have limitations. Existing nerve-muscle models are unable to combine human, cellular and genetic context with a functional outcome. LUMC and PimBio will use patient-derived reprogrammed cells to generate a new model to study nerve-muscle interactions in health and diseaseThis model will bridge the gap between 2D cell culture and animal models. 

They will combine the chip development technology from PimBio with the biological expertise on 3D cell culture and neuromuscular disorders to develop a chip that will provide researchers worldwide with a better tool to study neuromuscular disorders. As a proof of concept, they will use this chip to model the neuromuscular disorder myasthenia gravis. 

Summary
Successful communication between nerve and muscle is critical for enabling muscle contraction and ultimately life. LUMC and PimBio will develop a new model to study nerve-muscle interactions based on reprogrammed human cells and will use it to study disease mechanisms of neuromuscular disorders and their treatments.
Technology Readiness Level (TRL)
2 - 4
Time period
48 months
Partners
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