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

Kamel Mamchaoui, Capucine Trollet, Anne Bigot, Elisa Negroni, Soraya Chaouch, Annie Wolff, Prashanth K. Kandalla, Solenne Marie, James Di Santo, Jean L. St Guily, Francesco Muntoni, Jihee Kim, Susanne Philippi, Simone Spuler, Nicolas Levy, Sergiu C. Blumen, Thomas Voit, Woodring E. Wright, Ahmed Aamiri, Gillian Butler-BrowneVincent Mouly

Research output: Contribution to journalArticle

93 Citations (Scopus)

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.

Original languageEnglish (US)
Article number34
JournalSkeletal Muscle
Volume1
Issue number1
DOIs
StatePublished - Nov 1 2011

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Myoblasts
Cell Line
Muscles
Oculopharyngeal Muscular Dystrophy
Facioscapulohumeral Muscular Dystrophy
Cyclin-Dependent Kinase 4
Neuromuscular Diseases
Biological Therapy
Duchenne Muscular Dystrophy
Muscular Dystrophies
Telomerase
Muscle Cells
Stem Cells
Therapeutics
Animal Models
Transplantation
Pharmacology
Biopsy
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Orthopedics and Sports Medicine

Cite this

Mamchaoui, K., Trollet, C., Bigot, A., Negroni, E., Chaouch, S., Wolff, A., ... Mouly, V. (2011). Immortalized pathological human myoblasts: Towards a universal tool for the study of neuromuscular disorders. Skeletal Muscle, 1(1), [34]. https://doi.org/10.1186/2044-5040-1-34

Immortalized pathological human myoblasts : Towards a universal tool for the study of neuromuscular disorders. / Mamchaoui, Kamel; Trollet, Capucine; Bigot, Anne; Negroni, Elisa; Chaouch, Soraya; Wolff, Annie; Kandalla, Prashanth K.; Marie, Solenne; Di Santo, James; St Guily, Jean L.; Muntoni, Francesco; Kim, Jihee; Philippi, Susanne; Spuler, Simone; Levy, Nicolas; Blumen, Sergiu C.; Voit, Thomas; Wright, Woodring E.; Aamiri, Ahmed; Butler-Browne, Gillian; Mouly, Vincent.

In: Skeletal Muscle, Vol. 1, No. 1, 34, 01.11.2011.

Research output: Contribution to journalArticle

Mamchaoui, K, Trollet, C, Bigot, A, Negroni, E, Chaouch, S, Wolff, A, Kandalla, PK, Marie, S, Di Santo, J, St Guily, JL, Muntoni, F, Kim, J, Philippi, S, Spuler, S, Levy, N, Blumen, SC, Voit, T, Wright, WE, Aamiri, A, Butler-Browne, G & Mouly, V 2011, 'Immortalized pathological human myoblasts: Towards a universal tool for the study of neuromuscular disorders', Skeletal Muscle, vol. 1, no. 1, 34. https://doi.org/10.1186/2044-5040-1-34
Mamchaoui, Kamel ; Trollet, Capucine ; Bigot, Anne ; Negroni, Elisa ; Chaouch, Soraya ; Wolff, Annie ; Kandalla, Prashanth K. ; Marie, Solenne ; Di Santo, James ; St Guily, Jean L. ; Muntoni, Francesco ; Kim, Jihee ; Philippi, Susanne ; Spuler, Simone ; Levy, Nicolas ; Blumen, Sergiu C. ; Voit, Thomas ; Wright, Woodring E. ; Aamiri, Ahmed ; Butler-Browne, Gillian ; Mouly, Vincent. / Immortalized pathological human myoblasts : Towards a universal tool for the study of neuromuscular disorders. In: Skeletal Muscle. 2011 ; Vol. 1, No. 1.
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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.",
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AU - Chaouch, Soraya

AU - Wolff, Annie

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AU - St Guily, Jean L.

AU - Muntoni, Francesco

AU - Kim, Jihee

AU - Philippi, Susanne

AU - Spuler, Simone

AU - Levy, Nicolas

AU - Blumen, Sergiu C.

AU - Voit, Thomas

AU - Wright, Woodring E.

AU - Aamiri, Ahmed

AU - Butler-Browne, Gillian

AU - Mouly, Vincent

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