Journal
CELLS
Volume 10, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/cells10082169
Keywords
mesenchymal stem cell; exosomes; skeletal muscle; activin A
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Funding
- National Research Foundation of Korea (NRF) - Korea Government (MSIT) [NRF-2017R1E1A1A01073021, NRF-2020R1C1C1012769]
- EwhaWomans University
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This study investigated the role of T-MSC exosomes in recovery of body weight and skeletal muscle mass in chemotherapy-treated mice. The results showed that T-MSC exosomes rescued muscle atrophy both in vivo and in vitro via a miR-145-5p dependent manner, suggesting therapeutic potential in maintaining or improving skeletal muscle mass under various activin A elevated pathologic conditions.
Skeletal muscle mass is decreased under a wide range of pathologic conditions. In particular, 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.
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