title: Immortalized pathological human myoblasts: towards a universal tool for the study of neuromuscular disorders.
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.
authors: Thérapie des maladies du muscle strié, Institut de Myologie, UM76, UPMC Université Paris 6, Paris, France.|INSERM U974, Paris, France.|CNRS UMR 7215, Paris, France.
authors: Kamel
authors: K
authors: Mamchaoui
authors: Thérapie des maladies du muscle strié, Institut de Myologie, UM76, UPMC Université Paris 6, Paris, France.|INSERM U974, Paris, France.|CNRS UMR 7215, Paris, France.
authors: Capucine
authors: C
authors: Trollet
authors: Thérapie des maladies du muscle strié, Institut de Myologie, UM76, UPMC Université Paris 6, Paris, France.|INSERM U974, Paris, France.|CNRS UMR 7215, Paris, France.
authors: Anne
authors: A
authors: Bigot
authors: Thérapie des maladies du muscle strié, Institut de Myologie, UM76, UPMC Université Paris 6, Paris, France.|INSERM U974, Paris, France.|CNRS UMR 7215, Paris, France.
authors: Elisa
authors: E
authors: Negroni
authors: Thérapie des maladies du muscle strié, Institut de Myologie, UM76, UPMC Université Paris 6, Paris, France.|INSERM U974, Paris, France.|CNRS UMR 7215, Paris, France.
authors: Soraya
authors: S
authors: Chaouch
authors: Thérapie des maladies du muscle strié, Institut de Myologie, UM76, UPMC Université Paris 6, Paris, France.|INSERM U974, Paris, France.|CNRS UMR 7215, Paris, France.
authors: Annie
authors: A
authors: Wolff
authors: Thérapie des maladies du muscle strié, Institut de Myologie, UM76, UPMC Université Paris 6, Paris, France.|INSERM U974, Paris, France.|CNRS UMR 7215, Paris, France.
authors: Prashanth K
authors: PK
authors: Kandalla
authors: Thérapie des maladies du muscle strié, Institut de Myologie, UM76, UPMC Université Paris 6, Paris, France.|INSERM U974, Paris, France.|CNRS UMR 7215, Paris, France.
authors: Solenne
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authors: Marie
authors: Innate Immunity Unit, INSERM U 668, Institut Pasteur, Paris, France.
authors: James
authors: J
authors: Di Santo
authors: Thérapie des maladies du muscle strié, Institut de Myologie, UM76, UPMC Université Paris 6, Paris, France.|INSERM U974, Paris, France.|CNRS UMR 7215, Paris, France.|Service d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale, Faculté de Médecine St Antoine, Université Pierre et Marie Curie, Hôpital Tenon, Paris, France.
authors: Jean Lacau
authors: JL
authors: St Guily
authors: The Dubowitz Neuromuscular Centre, Institute of Child Health, University College, London, UK.
authors: Francesco
authors: F
authors: Muntoni
authors: The Dubowitz Neuromuscular Centre, Institute of Child Health, University College, London, UK.
authors: Jihee
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authors: Kim
authors: Thérapie des maladies du muscle strié, Institut de Myologie, UM76, UPMC Université Paris 6, Paris, France.|Muscle Research Unit, Experimental and Clinical Research Center, Charité University Hospital and Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors: Susanne
authors: S
authors: Philippi
authors: Muscle Research Unit, Experimental and Clinical Research Center, Charité University Hospital and Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors: Simone
authors: S
authors: Spuler
authors: Faculté de Médecine de Marseille, Université de la Méditerranée, Inserm UMRS 910 Génétique Médicale et Génomique Fonctionnelle, Marseille, France.
authors: Nicolas
authors: N
authors: Levy
authors: Department of Neurology, Hillel Yaffe Medical Center, PO Box 169, Hadera, 38100, Israel.
authors: Sergiu C
authors: SC
authors: Blumen
authors: Thérapie des maladies du muscle strié, Institut de Myologie, UM76, UPMC Université Paris 6, Paris, France.|INSERM U974, Paris, France.|CNRS UMR 7215, Paris, France.
authors: Thomas
authors: T
authors: Voit
authors: UT Southwestern Medical Center, Department of Cell Biology, Dallas, TX 75390, USA.
authors: Woodring E
authors: WE
authors: Wright
authors: Laboratoire LBCM, Departement de Biologie, Faculté des Sciences, Agadir, Maroc.
authors: Ahmed
authors: A
authors: Aamiri
authors: Thérapie des maladies du muscle strié, Institut de Myologie, UM76, UPMC Université Paris 6, Paris, France.|INSERM U974, Paris, France.|CNRS UMR 7215, Paris, France.
authors: Gillian
authors: G
authors: Butler-Browne
authors: Thérapie des maladies du muscle strié, Institut de Myologie, UM76, UPMC Université Paris 6, Paris, France.|INSERM U974, Paris, France.|CNRS UMR 7215, Paris, France.
authors: Vincent
authors: V
authors: Mouly