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Normal growth and regenerating ability of myoblasts from unaffected muscles of facioscapulohumeral muscular dystrophy patients

Gene Therapy volume 12, pages 1651–1662 (2005)Cite this article

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease characterized by a typical regional distribution, featuring composed patterns of clinically affected and unaffected muscles. No treatment is available for this condition, in which the pathophysiological mechanism is still unknown. Autologous transfer of myoblasts from unaffected to affected territories could be considered as a potential strategy to delay or stop muscle degeneration. To evaluate the feasibility of this concept, we explored and compared the growth and differentiation characteristics of myoblasts prepared from phenotypically unaffected muscles of five FSHD patients and 10 control donors. According to a clinically approved procedure, 109 cells of a high degree of purity were obtained within 16–23 days. More than 80% of these cells were myoblasts, as demonstrated by labeling of the muscle markers CD56 and desmin. FSHD myoblasts presented a doubling time equivalent to that of control cells; they kept high proliferation ability and did not show early telomere shortening. In vitro, these cells were able to differentiate and to express muscle-specific antigens. In vivo, they participated to muscle structures when injected into immunodeficient mice. These data suggest that myoblasts expanded from unaffected FSHD muscles may be suitable tools in view of autologous cell transplantation clinical trials.

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Acknowledgements

This work was supported by a grant from the ‘Association Française contre les Myopathies’ (AFM). This study has been promoted by the CHU de Nice. The production of control myoblasts was supported by both AFM and the ‘Assistance Publique-Hôpitaux de Paris’ (France). We thank Dr James Di Santo (Institut Pasteur, Paris) for the kind gift of the immunodeficient Rag mice, Dr Marc Jeanpierre for FSHD molecular diagnosis, Dr Vincent Mouly for telomere evaluation, Drs Gillian Buttler-Browne and Marc Fiszman for critical review of the manuscript, Drs Philippe Chaumet-Riffaud and Solange Solbes-Latourette for helpful assistance at setting this preclinical protocol and Miss Jessica Shama for helpful revision of the document. We thank the company Myosix SA and Mr Frédéric Chereau for giving access to the myoblast culture methodology. Finally, we would also like to thank all the patients for their participation to this study.

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Author notes

  1. J-T Vilquin, J-P Marolleau and S Sacconi: These authors contributed equally to this work

Authors and Affiliations

  1. Inserm U582, Groupe hospitalier Pitié-Salpêtrière, Institut de Myologie, Paris, France

    J-T Vilquin & I Garcin

  2. Laboratoire de Thérapie Cellulaire, Hôpital Saint Louis, Paris, France

    J-P Marolleau, M-N Lacassagne, I Robert, B Ternaux & J Larghero

  3. Inserm U638, CHU de Nice, Fédération des Maladies Neuromusculaires, Nice, France

    S Sacconi & C Desnuelle

  4. CNRS UMR 7000, Groupe hospitalier Pitié-Salpêtrière, Paris, France

    B Bouazza

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Vilquin, JT., Marolleau, JP., Sacconi, S. et al. Normal growth and regenerating ability of myoblasts from unaffected muscles of facioscapulohumeral muscular dystrophy patients. Gene Ther 12, 1651–1662 (2005). https://doi.org/10.1038/sj.gt.3302565

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