# Canine Adipose MSC-Derived Exosomes Ameliorate Skeletal Muscle Injury in Mice

## TL;DR

Canine fat cell exosomes help repair muscle injuries in mice, offering a new treatment for muscle atrophy and related issues in dogs.

## Contribution

This study demonstrates the therapeutic potential of canine adipose MSC-derived exosomes for treating skeletal muscle injury.

## Key findings

- cADMSC-Exos reduced muscle atrophy and improved myotube morphology in vitro.
- Exosomes significantly alleviated fibrosis and fatty infiltration in injured mouse muscle tissue.
- The treatment modulated atrophy-related proteins like MuRF1 and Atrogin-1.

## Abstract

Muscle injuries in dogs frequently lead to long-term complications such as muscle atrophy, with healthy muscle fibres being replaced by fatty or scar tissue. These changes will diminish the dog’s quality of life. However, current treatment options are limited. The aim of this study was to investigate whether the canine adipose mesenchymal stem cell-derived exosomes (cADMSC-Exos) possess therapeutic potential for muscle injury and dysfunction. cADMSCs and exosomes were successfully obtained and then identified. By establishing an in vitro model of C2C12 cell atrophy and a mouse muscle injury model, we demonstrated that cADMSC-Exos can ameliorate the adverse conditions of muscle atrophy, fibrosis, and fatty infiltration, exerting beneficial tissue-repairing effects. This lays the foundation for future research into the application of ‘cell-free’ medical technology for treating canine muscular disorders.

Severe skeletal muscle injury in dogs can result in muscle atrophy, fibrotic remodeling, and fat accumulation, leading to skeletal muscle dysfunction and impaired quality of life. However, there is currently no effective treatment available. This study aims to investigate the potential of canine adipose mesenchymal stem cell-derived exosomes (cADMSC-Exos) as a novel acellular therapy for the repair of muscle atrophy and injury. cADMSCs and their derived exosomes were isolated and characterized. A dexamethasone-induced C2C12 myotube atrophy model was established to evaluate the effects of cADMSC-Exos on muscle atrophy by assessing myotube morphology and the expression of atrophy-related factors. Subsequently, a glycerol-induced mouse muscle injury model was constructed. Through histological analysis and Western blot, the efficacy and safety of cADMSC-Exos in vivo were systematically evaluated. Results indicated that cADMSC-Exos demonstrated significant anti-atrophic activity in both two models, ameliorating skeletal muscle atrophy and the upregulation of muscle RING finger 1 (MuRF1) and muscle atrophy F-box (Atrogin-1) (p < 0.05), consistent with morphological alterations. Moreover, cADMSC-Exos markedly alleviated fibrosis and fatty infiltration in injured muscle tissue (p < 0.0001). Overall, these findings indicate that cADMSC-Exos promote muscle repair and attenuate pathological remodeling by modulating the local microenvironment and protein expression, highlighting their potential as a therapeutic strategy for muscular disorders.