Skeletal Muscle Satellite Cells in Amyotrophic Lateral Sclerosis

Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving progressive muscular paralysis reflecting degeneration of motor neurons. Skeletal muscle tissue seems to play a significant role in ALS pathogenesis. Here, the role of satellite cells (SCs) in ALS muscle atrophy is investigated. Methods: We isolated SCs from ALS human muscle biopsies and we analyzed their ability to grow and expand in vitro. Ultrastructural and immunophenotypical features were analyzed. Quantitative real-time RT-QPCR and western blot (WB) analyses were performed to evaluate MRFs and MyH1 expression. Results: ALS SCs showed a high proliferative potential, but their capacity to proceed through the myogenic program and form myotubes seems altered compared to controls (Ctrls). We observed that differentiating ALS SCs showed some specific features, but they displayed an altered morphology, with a large number of vacuoles. RT-QPCR and WB showed lower Myf-4 and MyH1 compared to Ctrls. Conclusions: Our data suggest that the capacity of ALS SCs to proceed through the myogenic program seems to be altered: SCs seem to lose their ability to regenerate and restore mature myofibers.