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Here, we demonstrate that extracellular vesicles derived from human pluripotent stem cell\u2010derived sacral neural crest cells (Sacral NC\u2010EVs) promote pelvic neuroregeneration by suppressing oxidative stress\u2010induced pyroptosis. In a rat model of major pelvic ganglion (MPG) injury, local administration of Sacral NC\u2010EVs improved gastrointestinal motility and partially restored rectal neural innervation and epithelial barrier integrity. Mechanistic analyses showed that MPG injury increased oxidative stress and activated the NLRP3\u2010caspase\u20101\u2010GSDMD pyroptosis pathway, whereas Sacral NC\u2010EVs attenuated both responses. Comparisons across EV sources showed that Sacral NC\u2010EVs more effectively suppressed oxidative stress and pyroptosis and increased PGP9.5\u2010positive and ChAT\u2010positive neuronal areas than mesenchymal stem cell\u2010derived EVs and vagal neural crest\u2010derived EVs. Proteomic and functional analyses implicated EV\u2010associated annexin A1 (ANXA1) as one contributor to the antioxidant and anti\u2010pyroptotic effects of Sacral NC\u2010EVs through FPR2 signaling. Collectively, our findings support Sacral NC\u2010EVs as a promising cell\u2010free strategy for pelvic neural repair by targeting the oxidative stress\u2010pyroptosis axis.<\/jats:p>","DOI":"10.1002\/advs.78321","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:09:59Z","timestamp":1792120199000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sacral Neural Crest\u2010Derived Extracellular Vesicles Promote Pelvic Ganglion Repair Through Anti\u2010Pyroptotic Effects Involving ANXA1\u2013FPR2 Signaling"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5125-5291","authenticated-orcid":false,"given":"Ting","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery The First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou Guangdong China"},{"name":"Center For Stem Cell Biology and Tissue Engineering Key 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