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

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.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.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.Muscular dystrophies constitute a heterogeneous group of genetic muscle diseases characterized by progressive muscle weakness, wasting and degeneration, some of these features are common to muscle aging [1,2]. Over the past few years, the genetics and pathophysiology of some of these diseases has been deciphered, stimulating the development of novel gene-based (or mRNA-based) (for example, gene therapy, exon-skipping or codon read-through), cell-based and pharmacological therapies [3], which can either target the mutation directly, or target the consequences of that mutation, such as muscle wasting, atrophy or denerv