MyoLine – a platform for the immortalization of human cells

Contacts: Vincent Mouly, Anne Bigot, Kamel Mamchaoui

With the development of innovative therapeutic approaches for neuromuscular diseases, such as gene therapy or genome editing, muscle cells isolated from patients, called myoblasts, represent an ideal in vitro model to assess these approaches. Using such cells allows to diminish the number of animal experimentations, but they also bear the exact mutation of the patient in its own genetic environment.

There are limits to these in vitro approaches: human somatic cells have a limited proliferative capacity regulated by the mitotic clock, and reach replicative senescence after a defined number of divisions. This limit in proliferation is reached even earlier in degenerative diseases. We can neutralize the replicative senescence of human muscle cells by using a double transduction with lentiviral vectors, thus making them immortal.

As of today, the platform for immortalization of human cells of the Institute of Myology had generated over 130 human myoblast cell lines isolated from patients suffering from over 27 different diseases (DMD, LGMD, FSHD, …), as well as from control subjects. Most of the original material has been obtained anonymously according to the legal requirements, in collaboration with MyoBank, affiliated to EuroBioBank.

Because access to muscle biopsies may be limited for some pathologies, we have also developed the immortalization of skin fibroblasts. These immortalized fibroblasts are then transduced by an inducible MyoD, a muscle specific transcription factor, and these myoconverted cells can then form myotubes and express muscle markers just like muscle cells.

Since several years, these cell lines are available to the scientific community on a collaborative basis, and many international laboratories already use them. A subset of these cell lines can also be used under MTAs for the development of therapeutic tools by private partners. Our efforts aim at encourage and facilitate researches on neuromuscular disorders, as well as the development on therapeutic strategies.

 

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