Neural Stem Cell – Derived small Extracellular Vesicles Ameliorate the Disease Progression in SOD1 G93A Murine Model

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily affects motor neurons, leading to muscle weakness, paralysis, and ultimately, respiratory failure. Extracellular vesicles (EVs) facilitate intercellular communication by mimicking the functions of their parent cells. In this study, we confirmed that repeated administration of neural stem cell - derived small extracellular vesicles (NSC-derived sEVs) improved motor performance and provided protection to lumbar motor neurons, the neuromuscular junctions, and muscle morphology in the SOD1 G93A transgenic mouse model. Furthermore, by analyzing the miRNA profiles of NSC-derived EVs and RNA-sequencing of muscle specimens from ALS-SOD1 patients, we demonstrated the rescue effects of NSC- derived EVs might be linked to the p53 pathway. Compared to the PBS group, both TP53 and the p53 upregulated modulator of apoptosis (puma) were downregulated in the spinal cord of mice treated with NSC-derived EVs. These data contribute by providing additional knowledge for the promising use of NSC-derived EVs as a potential therapy for ALS.