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This in vitro study aimed to evaluate the protective efficacy of ESC-sEVs against lead acetate (PbAc)-induced damage in cochlear spiral ganglion neurons (SGNs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cochlear SGNs of neonatal rats were primarily cultured and administrated with (i) serum-free medium (control); (ii) 25 \u03bcM PbAc; (iii) 0.05 \u03bcg\/\u03bcl ESC-sEVs (ESC-sEVs); (iv) 25 \u03bcM PbAc\u2009+\u20090.05 \u03bcg\/\u03bcl ESC-sEVs (PbAc\u2009+\u2009ESC-sEVs). After treatment, cell viability of SGNs was assessed by CCK-8 assay. The changes in levels of reactive oxygen species, lipid peroxides, and apoptosis were detected by immunofluorescence and flow cytometry. The protective mechanisms of ESC-sEVs against lead-induced SGNs damage were elucidated by RNA sequencing and western blot analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The findings revealed that ESC-sEVs significantly increased the viability of SGNs subjected to PbAc exposure. Immunofluorescence and flow cytometry revealed that ESC-sEVs effectively attenuated oxidative stress, lipid peroxidation, and apoptotic processes in PbAc-exposed SGNs. Furthermore, RNA sequencing and western blot analysis demonstrated that ESC-sEVs activated the PI3 K\/AKT signaling pathway, which plays a pivotal role in alleviating lead-induced neuronal injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In conclusion, this study provides the first evidence supporting the therapeutic potential of ESC-sEVs in addressing lead-induced ototoxicity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/00368504251358007","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T12:34:55Z","timestamp":1752064495000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Embryonic stem cell-derived small extracellular vesicles alleviate lead-induced cochlear spiral ganglion neurons injury by activating PI3 K\/AKT signaling 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(Xiangya Hospital), Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Xiangya Hospital, Central South University"},{"name":"Clinical Research Center for Women's Reproductive Health in Hunan Province, Changsha, Hunan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Xiangya Hospital, Central South University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"He","sequence":"additional","affiliation":[{"name":"Xiangya Hospital, Central South University"},{"name":"Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan, China"},{"name":"Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders in Hunan Province, Changsha, Hunan, China"},{"name":"National Clinical Research Center for Geriatric Disorders 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