Résumé :
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Communication n° 60 OBJECTIVE: To assess the biological properties of myogenic cells prepared from unaffected muscles of FSHD patients and compared them with that of FSHD affected muscles and matched control myoblasts in the perspective of an autologous myoblasts transfer clinical trial BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease linked to a deletion within tandem array of repeats termed D4Z4 located on chromosome 4q. It is characterized by a typical regional distribution, featuring composed pattern of affected and unaffected muscles. No treatment is currently available for this disease which physiopathological mechanism is still unknown. Autologous myoblast transfer from unaffected to affected territories could be considered in view of increasing the regenerating ability of affected muscles. METHODS: We produced 1) myoblasts from unaffected muscle of 5 FSHD patients and from the same muscles of 10 healthy controls; 2) myoblasts from affected shoulder girdle muscles of 4 FSHD patients and from the same muscles of 4 healthy controls. We evaluated in each FSHD cell culture at different time points: morphology, proliferation ability (proliferation rate, doubling time), purity of the cell culture (percentage of CD56 and desmin-positive cells), cell viability, telomere length and in vitro differentiation (myoblasts fusion index, expression of myosin heavy chain isoformes). RESULTS: Myoblasts prepared from unaffected muscles of FSHD patients presented no differences in morphology, proliferation ability and in vitro differentiation when compared to matched controls while myoblasts from affected muscles displayed several alterations. In particular, we could observe in these cells the appearance of "vacuolar-necrotic phenotype", reduced proliferation ability with a significant increase on cell doubling time and an impaired differentiation with an important reduction in myoblast fusion index. CONCLUSION: In contrast with myoblasts from affected FSHD muscle, myoblasts from unaffected territories presented no alteration when compared to controls. These findings could open the possibility of a future clinical trial on autologous myoblast transfer for FSHD patients.
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