Extracellular Vesicles from Regenerating Skeletal Muscle Mitigate Muscle Atrophy in an Amyotrophic Lateral Sclerosis Mouse Model
Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease characterized by progressive motor neuron degeneration and muscle atrophy, with no effective treatments available. Chronic inflammation, which impairs muscle regeneration and promotes proteolysis, is a key contributor to ALS-...
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| Format: | Article |
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MDPI AG
2025-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/14/6/464 |
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| author | Jinghui Gao Aria Sikal Rachel Hankin Yaochao Zheng Elijah Sterling Kenny Chan Yao Yao |
| author_facet | Jinghui Gao Aria Sikal Rachel Hankin Yaochao Zheng Elijah Sterling Kenny Chan Yao Yao |
| author_sort | Jinghui Gao |
| collection | DOAJ |
| description | Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease characterized by progressive motor neuron degeneration and muscle atrophy, with no effective treatments available. Chronic inflammation, which impairs muscle regeneration and promotes proteolysis, is a key contributor to ALS-related muscle atrophy and a promising therapeutic target. Here, we applied extracellular vesicles (EVs) derived from regenerating skeletal muscles 14 days post-acute injury (CTXD14SkM-EVs), which possess a unique anti-inflammatory profile, to target muscle defects in ALS. We found that CTXD14SkM-EVs enhanced myoblast differentiation and fusion in a cellular muscle-wasting model induced by pro-inflammatory cytokine tumor necrosis factor alpha. Intramuscular administration of these EVs into an ALS mouse model mitigated muscle atrophy by promoting muscle regeneration, shifting macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 state, and suppressing the aberrant Nuclear Factor Kappa B (NF-κB) signaling, a key driver of muscle protein degradation. These results underscore the therapeutic potential of regenerating muscle-derived EVs for combating muscle atrophy in ALS. |
| format | Article |
| id | doaj-art-a960a830a4994fcaa4dcad179e494830 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-a960a830a4994fcaa4dcad179e4948302025-08-20T03:43:15ZengMDPI AGCells2073-44092025-03-0114646410.3390/cells14060464Extracellular Vesicles from Regenerating Skeletal Muscle Mitigate Muscle Atrophy in an Amyotrophic Lateral Sclerosis Mouse ModelJinghui Gao0Aria Sikal1Rachel Hankin2Yaochao Zheng3Elijah Sterling4Kenny Chan5Yao Yao6Regenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Science, University of Georgia, Athens, GA 30602, USARegenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Science, University of Georgia, Athens, GA 30602, USARegenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Science, University of Georgia, Athens, GA 30602, USARegenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Science, University of Georgia, Athens, GA 30602, USARegenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Science, University of Georgia, Athens, GA 30602, USADepartment of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USARegenerative Bioscience Center, Department of Animal and Dairy Science, College of Agricultural and Environmental Science, University of Georgia, Athens, GA 30602, USAAmyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease characterized by progressive motor neuron degeneration and muscle atrophy, with no effective treatments available. Chronic inflammation, which impairs muscle regeneration and promotes proteolysis, is a key contributor to ALS-related muscle atrophy and a promising therapeutic target. Here, we applied extracellular vesicles (EVs) derived from regenerating skeletal muscles 14 days post-acute injury (CTXD14SkM-EVs), which possess a unique anti-inflammatory profile, to target muscle defects in ALS. We found that CTXD14SkM-EVs enhanced myoblast differentiation and fusion in a cellular muscle-wasting model induced by pro-inflammatory cytokine tumor necrosis factor alpha. Intramuscular administration of these EVs into an ALS mouse model mitigated muscle atrophy by promoting muscle regeneration, shifting macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 state, and suppressing the aberrant Nuclear Factor Kappa B (NF-κB) signaling, a key driver of muscle protein degradation. These results underscore the therapeutic potential of regenerating muscle-derived EVs for combating muscle atrophy in ALS.https://www.mdpi.com/2073-4409/14/6/464amyotrophic lateral sclerosisregenerating skeletal muscleextracellular vesiclesmuscle atrophy |
| spellingShingle | Jinghui Gao Aria Sikal Rachel Hankin Yaochao Zheng Elijah Sterling Kenny Chan Yao Yao Extracellular Vesicles from Regenerating Skeletal Muscle Mitigate Muscle Atrophy in an Amyotrophic Lateral Sclerosis Mouse Model Cells amyotrophic lateral sclerosis regenerating skeletal muscle extracellular vesicles muscle atrophy |
| title | Extracellular Vesicles from Regenerating Skeletal Muscle Mitigate Muscle Atrophy in an Amyotrophic Lateral Sclerosis Mouse Model |
| title_full | Extracellular Vesicles from Regenerating Skeletal Muscle Mitigate Muscle Atrophy in an Amyotrophic Lateral Sclerosis Mouse Model |
| title_fullStr | Extracellular Vesicles from Regenerating Skeletal Muscle Mitigate Muscle Atrophy in an Amyotrophic Lateral Sclerosis Mouse Model |
| title_full_unstemmed | Extracellular Vesicles from Regenerating Skeletal Muscle Mitigate Muscle Atrophy in an Amyotrophic Lateral Sclerosis Mouse Model |
| title_short | Extracellular Vesicles from Regenerating Skeletal Muscle Mitigate Muscle Atrophy in an Amyotrophic Lateral Sclerosis Mouse Model |
| title_sort | extracellular vesicles from regenerating skeletal muscle mitigate muscle atrophy in an amyotrophic lateral sclerosis mouse model |
| topic | amyotrophic lateral sclerosis regenerating skeletal muscle extracellular vesicles muscle atrophy |
| url | https://www.mdpi.com/2073-4409/14/6/464 |
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