MyoLine

Myoline : the immortalization platform

With the development of innovative therapies such as gene therapy, muscle stem cells isolated from patients, called myoblasts, represent ideal in vitro models for testing these therapeutic strategies. These cells have the advantage of carrying the patient’s exact mutation in his own genetic environment, and are thus precious tools which allow fast screening while reducing the number of experiments on animals.

One of the limitations of the cellular approach is that these human cells exhibit a limited proliferative capacity regulated by a mitotic clock, and enter replicative senescence after a few divisions. This limit of proliferation is even more important in degenerative pathologies. Using double transduction (hTERT and cdk4) with lentiviral vectors, we neutralize the replicative senescence of these cells and make them immortal (Mamchaoui et al Skel Muscle 2011). Today the immortalization platform of the Institute of Myology has generated more than 130 lines of human myoblasts from patients with more than 27 pathologies (DMD, LGMD, OPMD, FSHD, etc.) as well as from control subjects.

Because access to muscle biopsies remains very limited for many pathologies, we have also developed the immortalization of fibroblasts from skin biopsies of patients, using transduction by hTERT. Using lentiviral transduction of an inducible version of the myogenic factor MyoD, these cells are convertible into myoblasts and can fuse into myotubes like muscle cells do.

Since several years, these different lines have been made available to the international scientific community on the basis of collaborations, and a large number of international laboratories have used them. A subset of them can also be used with specific agreements (MTA) for the development of therapeutic tools by private partners. The aim of this approach is to encourage and promote research on neuromuscular diseases and the development of therapeutic strategies.

Exemples of lines: CellsMyoline