Muscle-on-chip model with fibroadipogenic progenitors and electrical impedance sensing

Generation of a human skeletal muscle-on-chip model containing extracellular matrix-producing fibroadipogenic progenitors and electrical impedance sensing

In a partnership between LUMC, Erasmus MC, and Optics11 B.V., technology will be developed to measure changes in the composition and architecture of in vitro engineered human 3D muscles, generated from patients with facioscapulohumeral muscular dystrophy (FSHD) and Pompe disease.

A major problem in developing therapies for skeletal muscle disorders is the limited availability and translatability of current human model systems for preclinical research. This has a large impact on society.

This project will generate a device suitable for measuring muscle contractility and electrical impedance in in vitro engineered human 3D muscles consisting of skeletal muscle cells and fibroadipogenic progenitors (FAPs) for FSHD and Pompe disease. 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 to establish long-term effects of treatments and the optimisation of treatment regimens. Since they use patient-derived cells, they can develop personalised models.

Deliverables include: (1) validated muscle-on-chip device with integrated contractile force and electrical impedance sensing; (2) list of extracellular matrix components produced by healthy, FSHD and Pompe disease in vitro engineered human 3D muscles containing skeletal muscle cells only; (3) protocols for the generation of FAPs established from human induced pluripotent stem cells and for the generation of in vitro engineered human 3D muscles consisting of skeletal muscle cells and FAPs; (5) consequences of the addition of FAPs on contractile force, electrical impedance, muscle integrity, and muscle fiber types. This project will provide a unique novel device for the study of disease mechanisms in skeletal muscle disorders and will aid in the development and testing of treatment options for skeletal muscle disorders.

In muscle diseases, fibroadipogenic progenitors are responsible for fibrosis and fatty replacement. In this project, they will generate advanced 3D models of muscle diseases in vitro and investigate the influence of fibroadipogenic progenitors on disease progression, muscle pathology, fibrosis, and fatty replacement.
Technology Readiness Level (TRL)
2 - 4
Time period
48 months