P02

The development of innovative and tailor-made therapies for neuromuscular diseases requires easy-to-use and suitable cellular models. Muscle stem cells derived from patients, known as myoblasts provide an ideal in vitro model that includes the genetic environment of each mutation. Their use is however restricted by their limited proliferative capacity, especially in degenerative diseases. We have therefore developed a strategy to immortalize myoblasts derived from muscle biopsies of dystrophic patients and generated more than 174 human immortalized myoblast lines including 36 neuromuscular diseases such as DMD, DM1, LGMDR2, OPMD, FSHD and control subjects. Whenever access to muscle biopsies is not possible, we use human skin fibroblasts: in addition to immortalization, we use the conditional expression of the myogenic factor MyoD which drives the muscle conversion and differentiation into multinucleated myotubes.

In recent years, Fibro-Adipogenic Progenitors (FAPs) have been described as key cell players during muscle homeostasis, regeneration and in fibrotic conditions. To support investigations in this field, we have already generated immortalized FAPs isolated from muscles of DMD and control subjects and we are currently developing immortalized FAPs for other diseases.

We have also recently tested CRISPR-Cas9 tools on our human immortalized muscle cell lines and succeeded in efficient generation of KO cells. These tools will potentially allow the generation of isogenic cell lines.

Our cellular models are available to the academic international scientific community on a collaborative basis, and to private entities upon dedicated MTAs. The Myoline platform can also be solicited to set up new cellular models on request.