Mesenchymal stem cell‐derived exosomes protect muscle loss by mir‐145‐5p activity targeting activin a receptors

Skeletal muscle mass is decreased under a wide range of pathologic conditions. In partic-ular, chemotherapy is well known for inducing muscle loss and atrophy. Previous studies using tonsil‐derived mesenchymal stem cells (T‐MSCs) or a T‐MSC‐conditioned medium showed effective recovery of total body weight in the chemotherapy‐preconditioned bone marrow transplantation mouse model. This study investigated whether extracellular vesicles of T‐MSCs, such as exosomes, are a key player in the recovery of body weight and skeletal muscle mass in chemotherapy‐treated mice. T‐MSC exosomes transplantation significantly decreased loss of total body weight and muscle mass in the busulfan‐cyclophosphamide conditioning regimen in BALB/c recipient mice containing elevated serum activin A. Additionally, T‐MSC exosomes rescued impaired C2C12 cell differentiation in the presence of activin A in vitro. We found that T‐MSC exosomes possess abundant miR‐ 145‐5p, which targets activin A receptors, ACVR2A, and ACVR1B. Indeed, T‐MSC exosomes rescue muscle atrophy both in vivo and in vitro via miR‐145‐5p dependent manner. These results suggest that T‐MSC exosomes have therapeutic potential to maintain or improve skeletal muscle mass in various activin A elevated pathologic conditions.