Immortalized pathological human myoblasts: towards a universal tool for the study of neuromuscular disordersReport as inadecuate

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Skeletal Muscle

, 1:34

First Online: 01 November 2011Received: 20 June 2011Accepted: 01 November 2011


BackgroundInvestigations 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.

MethodsUsing 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.

ResultsThe 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.

ConclusionsDystrophic 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.

List of abbreviationsAONsantisense oligonucleotides

CDK-4cyclin-dependent kinase 4

CMDcongenital muscular dystrophy

DMDDuchenne muscular dystrophy

DMEMDulbecco-s modified Eagle-s medium

FCSfetal calf serum

FSHDfacioscapulohumeral muscular dystrophy

hTERThuman telomerase reverse transcriptase

LGMD2Blimb-girdle muscular dystrophy type 2b

N-CAMneural cell adhesion molecule

OPMDoculopharyngeal muscular dystrophy

PBSphosphate-buffered serum

PCRpolymerase chain reaction.

Electronic supplementary materialThe online version of this article doi:10.1186-2044-5040-1-34 contains supplementary material, which is available to authorized users.

Kamel Mamchaoui, Capucine Trollet contributed equally to this work.

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Author: Kamel Mamchaoui - Capucine Trollet - Anne Bigot - Elisa Negroni - Soraya Chaouch - Annie Wolff - Prashanth K Kandalla - So


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