P176 Immortalized human muscle cells: easy-to-use models to study neuromuscular diseases

• Published in: Neuromuscular disorders : NMD Vol. 33; p. S109
• Main Authors: Butler-Browne, G., Ohana, J., Mamchaoui, K., Bensalah, M., Negroni, E., Trollet, C., Bigot, A., Mouly, V.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2023
• ISSN: 0960-8966; 1873-2364
• DOI: 10.1016/j.nmd.2023.07.176

In recent years, therapeutic approaches for neuromuscular diseases have been developed and new strategies are currently emerging. Human cellular models adapted to each disease and each mutation, are needed to test these therapeutic strategies. Patient-derived muscle stem cells, also known as myoblasts can be isolated from biopsies, but their use is restricted by 1) the availability of muscle biopsies for research, 2) the limited proliferative capacity of the myoblasts and 3) their potential exhaustion in degenerative diseases. The Myoline platform of the Center of Research in Myology develops easy-to-use immortalized human myoblast models isolated from muscle tissue of patients suffering from various neuromuscular diseases. When access to muscle biopsies is not available, fibroblasts from skin biopsies can be immortalized and converted into muscle cells. Recently, we are also developing models of Fibro-Adipogenic Progenitors (FAPS) from muscles of patients with neuromuscular diseases. Human muscle cells are immortalized by transduction of the telomerase (hTERT) and cyclin-dependent kinase 4 (cdk4) genes. These immortalized muscle cells present an extended proliferation, and retain their ability to differentiate and fuse into myotubes. We have generated more than 168 human immortalized myoblast lines including 36 neuromuscular diseases such as DMD, DM1, LGMD2B, OPMD, FSHD and control subjects. Whenever access to muscle biopsies is not possible, an alternative cellular model has been developed using human skin fibroblasts: the transduction with hTERT provides an extended proliferation, while the conditional expression of the myogenic factor MyoD drives the muscle conversion and differentiation into multinucleated myotubes. Several human fibroblast lines have been produced, e.g. from DMD, DM1 or controls subjects. These cellular models have the great advantage of being easy to use and allow rapid testing of therapeutic strategies. They are made available to the academic international scientific community on a collaborative basis. For some of these cell lines, the patient consent allows their use by private companies. The Myoline platform can also be solicited to set up new models on request.