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Open Access Research

Immortalized pathological human myoblasts: towards a universal tool for the study of neuromuscular disorders

Kamel Mamchaoui123, Capucine Trollet123, Anne Bigot123, Elisa Negroni123, Soraya Chaouch123, Annie Wolff123, Prashanth K Kandalla123, Solenne Marie123, James Di Santo4, Jean Lacau St Guily1235, Francesco Muntoni6, Jihee Kim6, Susanne Philippi17, Simone Spuler7, Nicolas Levy8, Sergiu C Blumen9, Thomas Voit123, Woodring E Wright10, Ahmed Aamiri11, Gillian Butler-Browne123 and Vincent Mouly123*

Author Affiliations

1 Thérapie des maladies du muscle strié, Institut de Myologie, UM76, UPMC Université Paris 6, Paris, France

2 INSERM U974, Paris, France

3 CNRS UMR 7215, Paris, France

4 Innate Immunity Unit, INSERM U 668, Institut Pasteur, Paris, France

5 Service d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale, Faculté de Médecine St Antoine, Université Pierre et Marie Curie, Hôpital Tenon, Paris, France

6 The Dubowitz Neuromuscular Centre, Institute of Child Health, University College, London, UK

7 Muscle Research Unit, Experimental and Clinical Research Center, Charité University Hospital and Max Delbrück Center for Molecular Medicine, Berlin, Germany

8 Faculté de Médecine de Marseille, Université de la Méditerranée, Inserm UMRS 910 Génétique Médicale et Génomique Fonctionnelle, Marseille, France

9 Department of Neurology, Hillel Yaffe Medical Center, PO Box 169, Hadera, 38100, Israel

10 UT Southwestern Medical Center, Department of Cell Biology, Dallas, TX 75390, USA

11 Laboratoire LBCM, Departement de Biologie, Faculté des Sciences, Agadir, Maroc

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Skeletal Muscle 2011, 1:34  doi:10.1186/2044-5040-1-34

Published: 1 November 2011

Abstract

Background

Investigations into both the pathophysiology and therapeutic targets in muscle dystrophies have been hampered by the limited proliferative capacity of human myoblasts. Isolation of reliable and stable immortalized cell lines from patient biopsies is a powerful tool for investigating pathological mechanisms, including those associated with muscle aging, and for developing innovative gene-based, cell-based or pharmacological biotherapies.

Methods

Using transduction with both telomerase-expressing and cyclin-dependent kinase 4-expressing vectors, we were able to generate a battery of immortalized human muscle stem-cell lines from patients with various neuromuscular disorders.

Results

The immortalized human cell lines from patients with Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, oculopharyngeal muscular dystrophy, congenital muscular dystrophy, and limb-girdle muscular dystrophy type 2B had greatly increased proliferative capacity, and maintained their potential to differentiate both in vitro and in vivo after transplantation into regenerating muscle of immunodeficient mice.

Conclusions

Dystrophic cellular models are required as a supplement to animal models to assess cellular mechanisms, such as signaling defects, or to perform high-throughput screening for therapeutic molecules. These investigations have been conducted for many years on cells derived from animals, and would greatly benefit from having human cell models with prolonged proliferative capacity. Furthermore, the possibility to assess in vivo the regenerative capacity of these cells extends their potential use. The innovative cellular tools derived from several different neuromuscular diseases as described in this report will allow investigation of the pathophysiology of these disorders and assessment of new therapeutic strategies.