{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T03:32:41Z","timestamp":1783308761261,"version":"3.54.6"},"reference-count":40,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2023YFD180110"],"award-info":[{"award-number":["2023YFD180110"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>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 &lt; 0.05), consistent with morphological alterations. Moreover, cADMSC-Exos markedly alleviated fibrosis and fatty infiltration in injured muscle tissue (p &lt; 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.<\/jats:p>","DOI":"10.3390\/ani16050855","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T15:49:42Z","timestamp":1773071382000},"page":"855","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Canine Adipose MSC-Derived Exosomes Ameliorate Skeletal Muscle Injury in Mice"],"prefix":"10.3390","volume":"16","author":[{"given":"Jiaxuan","family":"Gao","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujue","family":"Li","sequence":"additional","affiliation":[{"name":"Veterinary Teaching Hospital, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yougang","family":"Zhong","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1053\/j.tcam.2013.11.001","article-title":"Introduction to myofascial trigger points in dogs","volume":"29","author":"Wall","year":"2014","journal-title":"Top. Companion Anim. Med."},{"key":"ref_2","first-page":"196","article-title":"Iliopsoas strain demographics, concurrent injuries, and grade determined by musculoskeletal ultrasound in 72 agility dogs","volume":"87","author":"Sack","year":"2023","journal-title":"Can. J. Vet. Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Krystalli, A., Papaefthymiou, S., Panteli, K., Sideri, A., Pappa, E.I., and Prassinos, N.N. (2024). Fibrotic Contracture of the Infraspinatus Muscle with or without Contracture of the Teres Minor Muscle: A Retrospective Study in Eight Dogs. Animals, 14.","DOI":"10.3390\/ani14172589"},{"key":"ref_4","first-page":"255","article-title":"Quantitative assessment of muscle in dogs using a vertebral epaxial muscle score","volume":"81","author":"Freeman","year":"2017","journal-title":"Can. J. Vet. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.tvjl.2015.07.005","article-title":"Age related skeletal muscle atrophy and upregulation of autophagy in dogs","volume":"206","author":"Pagano","year":"2015","journal-title":"Vet. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"rbaf050","DOI":"10.1093\/rb\/rbaf050","article-title":"Advancements in skeletal muscle tissue engineering: Strategies for repair and regeneration of skeletal muscle beyond self-repair","volume":"12","author":"Qi","year":"2025","journal-title":"Regen. Biomater."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e649","DOI":"10.1002\/mco2.649","article-title":"Skeletal muscle: Molecular structure, myogenesis, biological functions, and diseases","volume":"5","author":"Feng","year":"2024","journal-title":"MedComm"},{"key":"ref_8","first-page":"95","article-title":"Sarcopenia and Ageing","volume":"103","author":"Cheng","year":"2023","journal-title":"Biochemistry and Cell Biology of Ageing: Part IV, Clinical Science"},{"key":"ref_9","first-page":"241","article-title":"Semitendinosus myopathy and treatment with adipose-derived stem cells in working German shepherd police dogs","volume":"58","author":"Gibson","year":"2017","journal-title":"Can. Vet. J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Tsai, F.C., and Alvarez, L.X. (2024). Outcome of eight working dogs with fibrotic myopathy following extracorporeal shockwave and rehabilitation therapy: A case series. Front. Vet. Sci., 10.","DOI":"10.3389\/fvets.2023.1258319"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1186\/s13287-022-03076-8","article-title":"The therapeutic potential of Camel Wharton jelly mesenchymal stem cells (CWJ-MSCs) in canine chronic kidney disease model","volume":"13","author":"Farghali","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Al Delfi, I.R.T., Wood, C.R., Johnson, L.D.V., Snow, M.D., Innes, J.F., Myint, P., and Johnson, W.E.B. (2020). An In Vitro Comparison of the Neurotrophic and Angiogenic Activity of Human and Canine Adipose-Derived Mesenchymal Stem Cells (MSCs): Translating MSC-Based Therapies for Spinal Cord Injury. Biomolecules, 10.","DOI":"10.3390\/biom10091301"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Saba, E., Sandhu, M.A., and Pelagalli, A. (2024). Canine Mesenchymal Stromal Cell Exosomes: State-of-the-Art Characterization, Functional Analysis and Applications in Various Diseases. Vet. Sci., 11.","DOI":"10.3390\/vetsci11050187"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"116733","DOI":"10.1016\/j.lfs.2019.116733","article-title":"Human umbilical cord mesenchymal stem cells derived-exosomes in diseases treatment","volume":"233","author":"Yaghoubi","year":"2019","journal-title":"Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s12964-022-00959-4","article-title":"A review on exosomes application in clinical trials: Perspective, questions, and challenges","volume":"20","author":"Rezaie","year":"2022","journal-title":"Cell Commun. Signal."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.7150\/thno.22958","article-title":"Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis","volume":"8","author":"Chen","year":"2018","journal-title":"Theranostics"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sergazy, S., Adekenov, S., Khabarov, I., Adekenova, K., Maikenova, A., and Aljofan, M. (2025). Harnessing Mammalian- and Plant-Derived Exosomes for Drug Delivery: A Comparative Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26104857"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"332","DOI":"10.3934\/Neuroscience.2023026","article-title":"Improvement of spinal cord injury symptoms by targeting the Bax\/Bcl2 pathway and modulating TNF-\u03b1\/IL-10 using Platelet-Rich Plasma exosomes loaded with dexamethasone","volume":"10","author":"Naderi","year":"2023","journal-title":"AIMS Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4267","DOI":"10.1002\/jcb.26077","article-title":"Exosomes Transfer Among Different Species Cells and Mediating miRNAs Delivery","volume":"118","author":"Zhou","year":"2017","journal-title":"J. Cell. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1186\/s13287-025-04477-1","article-title":"Human umbilical cord-derived mesenchymal stromal cell exosomes ameliorate aging-associated skeletal muscle atrophy and dysfunction in SAMP10 mice","volume":"16","author":"Huang","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"ref_21","first-page":"23","article-title":"Human umbilical cord mesenchymal stem cell-derived exosomes ameliorate muscle atrophy via the miR-132-3p\/FoxO3 axis","volume":"49","author":"Ma","year":"2024","journal-title":"J. Orthop. Transl."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zhan, X.-S., El-Ashram, S., Luo, D.-Z., Luo, H.-N., Wang, B.-Y., Chen, S.-F., Bai, Y.-S., Chen, Z.-S., Liu, C.-Y., and Ji, H.-Q. (2019). A Comparative Study of Biological Characteristics and Transcriptome Profiles of Mesenchymal Stem Cells from Different Canine Tissues. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061485"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Phyo, H., Aburza, A., Mellanby, K., and Esteves, C.L. (2023). Characterization of canine adipose- and endometrium-derived Mesenchymal Stem\/Stromal Cells and response to lipopolysaccharide. Front. Vet. Sci., 10.","DOI":"10.3389\/fvets.2023.1180760"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Siriarchavatana, P., Oontawee, S., Rodprasert, W., Thongsit, A., Somparn, P., Na Nan, D., Nedumpun, T., Osathanon, T., Egusa, H., and Srisuwatanasagul, S. (2025). Small extracellular vesicles produced from canine adipose-derived mesenchymal stem cells mitigate diabetes mellitus in streptozotocin-induced mice via \u03b2-cell revitalization. BMC Vet. Res., 21.","DOI":"10.1186\/s12917-025-05042-x"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"238","DOI":"10.12688\/wellcomeopenres.18251.1","article-title":"The skeletal muscle phenotype of the DE50-MD dog model of Duchenne muscular dystrophy","volume":"7","author":"Hildyard","year":"2022","journal-title":"Wellcome Open Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kho, A.T., Kang, P.B., Kohane, I.S., and Kunkel, L.M. (2006). Transcriptome-scale similarities between mouse and human skeletal muscles with normal and myopathic phenotypes. BMC Musculoskelet. Disord., 7.","DOI":"10.1186\/1471-2474-7-23"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1292\/jvms.21-0325","article-title":"Quantitative assessment of muscle mass and gene expression analysis in dogs with glucocorticoid-induced muscle atrophy","volume":"84","author":"Yoshida","year":"2022","journal-title":"J. Vet. Med. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1113\/JP279595","article-title":"Infiltration of intramuscular adipose tissue impairs skeletal muscle contraction","volume":"598","author":"Biltz","year":"2020","journal-title":"J. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Mocchi, M., Dotti, S., Bue, M.D., Villa, R., Bari, E., Perteghella, S., Torre, M.L., and Grolli, S. (2020). Veterinary Regenerative Medicine for Musculoskeletal Disorders: Can Mesenchymal Stem\/Stromal Cells and Their Secretome Be the New Frontier?. Cells, 9.","DOI":"10.3390\/cells9061453"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"106123","DOI":"10.1016\/j.tvjl.2024.106123","article-title":"Mobility, functionality and functional mobility: A review and application for canine veterinary patients","volume":"305","author":"Wells","year":"2024","journal-title":"Vet. J."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Luo, H., Li, D., Chen, Z., Wang, B., and Chen, S. (2021). Manufacturing and banking canine adipose-derived mesenchymal stem cells for veterinary clinical application. BMC Vet. Res., 17.","DOI":"10.1186\/s12917-021-02791-3"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1186\/s13287-025-04747-y","article-title":"Mesenchymal stem cell-derived exosomes as cell-free therapeutics: Mechanistic insights and engineering strategies for liver disease treatment","volume":"16","author":"Yu","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Li, Z., Liu, C., Li, S., Li, T., Li, Y., Wang, N., Bao, X., Xue, P., and Liu, S. (2021). BMSC-Derived Exosomes Inhibit Dexamethasone-Induced Muscle Atrophy via the miR-486-5p\/FoxO1 Axis. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.681267"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Chen, R., Zheng, Y., Zhou, C., Dai, H., Wang, Y., Chu, Y., and Luo, J. (2024). N-Acetylcysteine Attenuates Sepsis-Induced Muscle Atrophy by Downregulating Endoplasmic Reticulum Stress. Biomedicines, 12.","DOI":"10.3390\/biomedicines12040902"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"de Souza, A.L.G., Alves, A.L.R., Martinez, C.G., de Sousa, J.C., and Kurtenbach, E. (2025). Biomarkers of Skeletal Muscle Atrophy Based on Atrogenes Evaluation: A Systematic Review and Meta-Analysis Study. Int. J. Mol. Sci., 26.","DOI":"10.37766\/inplasy2025.2.0089"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e14053","DOI":"10.7717\/peerj.14053","article-title":"Macrophages play a key role in tissue repair and regeneration","volume":"10","author":"Yu","year":"2022","journal-title":"PeerJ"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1002\/2211-5463.13504","article-title":"Myoblast-derived exosomes promote the repair and regeneration of injured skeletal muscle in mice","volume":"12","author":"Ji","year":"2022","journal-title":"FEBS Open Bio"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1186\/s13287-023-03555-6","article-title":"Polarized macrophages regulate fibro\/adipogenic progenitor (FAP) adipogenesis through exosomes","volume":"14","author":"Liu","year":"2023","journal-title":"Stem Cell Res. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/s42003-020-0830-7","article-title":"Spatial and temporal tracking of cardiac exosomes in mouse using a nano-luciferase-CD63 fusion protein","volume":"3","author":"Luo","year":"2020","journal-title":"Commun. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Hussain, S., Ijaz, S., Wajid, A., Qadeer, A., Suliman, M., Alzahrani, F.M., Alzahrani, K.J., Alsharif, K.F., Chang, C.-W., and Chen, C.-C. (2025). Decoding the functional plasticity of milk-derived exosomes: Implications for nutrition, immunity, and therapy. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1645355"}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/5\/855\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T05:23:35Z","timestamp":1773206615000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/5\/855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,9]]},"references-count":40,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ani16050855"],"URL":"https:\/\/doi.org\/10.3390\/ani16050855","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,9]]}}}