{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T10:05:44Z","timestamp":1770545144007,"version":"3.49.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2026,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n Introduction\/Aims<\/jats:title>\n \n Denervation\u2010induced muscle atrophy lacks effective therapies. Adipose\u2010derived stem cells (\n ADSCs<\/jats:styled-content>\n ) show promise for tissue repair. This study aimed to evaluate the effect of local\n ADSC<\/jats:styled-content>\n delivery on denervated muscle, investigate underlying mechanisms, and track\n ADSC<\/jats:styled-content>\n distribution and migration in\u00a0vivo.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In a mouse model of sciatic nerve transection and immediate reverse autograft repair,\n ADSCs<\/jats:styled-content>\n or phosphate\u2010buffered saline (\n PBS<\/jats:styled-content>\n ) were injected into the right gastrocnemius following nerve injury. Magnetic resonance imaging (\n MRI<\/jats:styled-content>\n ) and in\u00a0vivo imaging system (\n IVIS<\/jats:styled-content>\n ) tracked\n ADSC<\/jats:styled-content>\n migration. Muscle strength and gastrocnemius mass were measured. Histology (H&E, Masson), immunostaining (\n MyoD<\/jats:styled-content>\n ,\n CD163<\/jats:styled-content>\n ), and the real\u2010time reverse transcription polymerase chain reaction (\n RT<\/jats:styled-content>\n \u2010\n PCR<\/jats:styled-content>\n ) assessed fiber size, fibrosis, muscle regeneration,\n M2<\/jats:styled-content>\n macrophage infiltration, and inflammatory gene expression. Endpoints were measured 1\u2009week after the final injection (4\u2009weeks post\u2010injury).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n IVIS<\/jats:styled-content>\n showed that injected\n ADSCs<\/jats:styled-content>\n were visualized for 3\u20135\u2009days in\u00a0vivo while\n MRI<\/jats:styled-content>\n localized cells predominantly to the quadriceps and knee regions.\n ADSC<\/jats:styled-content>\n treatment increased normalized muscle strength (\n p<\/jats:italic>\n \u2009<\u20090.05), normalized gastrocnemius muscle weight (\n p<\/jats:italic>\n \u2009<\u20090.001) and fiber diameter (\n p<\/jats:italic>\n \u2009<\u20090.05); downregulated\n MMP2<\/jats:styled-content>\n expression (\n p<\/jats:italic>\n \u2009<\u20090.001), enhanced\n MyoD<\/jats:styled-content>\n + cell count (\n p<\/jats:italic>\n \u2009<\u20090.001), and promoted\n M2<\/jats:styled-content>\n macrophage infiltration (\n CD163<\/jats:styled-content>\n + cells,\n p<\/jats:italic>\n \u2009<\u20090.05;\n ARG1 mRNA<\/jats:styled-content>\n ,\n p<\/jats:italic>\n \u2009<\u20090.05).\n RT<\/jats:styled-content>\n \u2010\n PCR<\/jats:styled-content>\n revealed reduced pro\u2010inflammatory transcripts (\n IL<\/jats:styled-content>\n \u20106,\n IL<\/jats:styled-content>\n \u20101b;\n p<\/jats:italic>\n \u2009<\u20090.05).\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n ADSCs<\/jats:styled-content>\n ameliorate denervation\u2010induced muscle atrophy by improving muscle function and structure via\n M2<\/jats:styled-content>\n macrophage infiltration,\n MyoD<\/jats:styled-content>\n upregulation,\n MMP2<\/jats:styled-content>\n inhibition, and reduced inflammation. These findings underscore the therapeutic potential of\n ADSCs<\/jats:styled-content>\n for mitigating muscle atrophy following nerve injury, although the acute injury model used may not fully represent chronic clinical denervation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mus.70094","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T04:07:14Z","timestamp":1765339634000},"page":"329-339","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adipose\u2010Derived Stem Cells Alleviate Denervation\u2010Induced Muscle Atrophy by Promoting\n M2<\/scp>\n Macrophage Polarization and Reducing Inflammation"],"prefix":"10.1002","volume":"73","author":[{"given":"Qiannan","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Graduate School of Medicine Kyoto University Kyoto 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University Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michiharu","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery, Graduate School of Medicine Kyoto University Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shino","family":"Higai","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Jichi Medical University Tochigi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Toyohara","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Jichi Medical University Tochigi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Kuchimaru","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Jichi Medical University Tochigi 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