Forces of muscle cells in three-dimensional models of muscle disorders

Myofiber and myofibril contractility in hiPSC-derived 3D muscle for Pompe disease and facioscapulohumeral muscular dystrophy

In a partnership between Erasmus MC, LUMC, Amsterdam UMC, and IonOptix B.V., technology will be developed to measure the contractile forces in the contractile units of muscle-on-chip models, generated from patients with the skeletal muscle disorders Pompe disease and Facioscapulohumeral muscular dystrophy (FSHD).

Very few therapies for patients with one of >700 neuromuscular disorders exist, largely due to the lack of suitable human model systems. This has a large impact on society.

This project will generate a system suitable for measuring myofibril contractility in in vitro engineered human 3D muscle for Pompe disease and FSHD. The system will also be applicable to other neuromuscular disorders. The development of this advanced in vitro model will be important for basic researchers focusing on disease mechanisms and for translational researchers focusing on developing and testing therapeutic strategies. The muscle-on-chip model will reduce animal experiments and ultimately costs. The model will further allow establishing long-term effects of treatments and the optimisation of treatment regimens. Since patient-derived cells are used, personalised models can be developed that may prevent unnecessary treatment and ultimately reduce costs.

Deliverables include: (1) develop the system to measure myofibril contractility, optimise conditions to isolate myofibers and myofibrils from the muscle-on-chip model, and perform contractility assays; (2) enhance and characterise maturation of the current muscle-on-chip model; (3) characterise the defects underlying contractile force generation in Pompe disease and FSHD. This project will provide a unique novel tool for the study of disease mechanisms and treatment options to assess the effects on muscle contraction in human patient-derived engineered muscle.

In muscle diseases, muscle fibers lose their capacity to contract, resulting in loss of mobility and respiration. In this project advanced 3D models of muscle diseases in vitro will be generated and the effects will be investigated on the smallest contractile unit present in muscle cells using highly sensitive force measurements.
Technology Readiness Level (TRL)
2 - 4
Time period
36 months
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