Satellite Cell‐Derived Exosomes: A Novel Approach to Alleviate Skeletal Muscle Atrophy and Fibrosis

Abstract Skeletal muscle atrophy coincides with extensive fibrous tissue hyperplasia in muscle‐atrophied patients, and fibrous tissue plays a vital role in skeletal muscle function and hinders muscle fiber regeneration. However, effective drugs to manage skeletal muscle atrophy and fibrosis remain elusive. This study isolated and characterized exosomes derived from skeletal muscle satellite cells (MuSC‐Exo). The study investigated their effects on denervated skeletal muscle atrophy and fibrosis in Sprague Dawley (SD) rats via intramuscular injection. MuSC‐Exo demonstrated the potential to alleviate skeletal muscle atrophy and fibrosis. The underlying mechanism using single‐cell RNA sequencing data and functional analysis are analyzed. Mechanistic studies reveal close associations between fibroblasts and myoblasts, with the transforming growth factor β1 (TGF‐β1)‐Smad3‐Pax7 axis governing fibroblast activation in atrophic skeletal muscle. MuSC‐Exo intervention inhibited the TGF‐β1/Smad3 pathway and improved muscle atrophy and fibrosis. In conclusion, MuSC‐Exo‐based therapy may represent a novel strategy to alleviate skeletal muscle atrophy and reduce excessive fibrotic tissue by targeting Pax7 through the TGF‐β1/Smad3 pathway.