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Despite the slow self-regeneration of the peripheral nervous system and advances in surgery, complete recovery after nerve injury remains elusive especially when there is loss of substance. Human olfactory ecto-mesenchymal stem cells (OEMSC) have potential for the treatment of peripheral nerve injury through the secretion of bioactive factors, such as proteins, cytokines, chemokines as well as the release of extracellular vesicles (EV). The current research investigates the therapeutic effects of a venous bridge, filled with freshly purified or cryoconserved OEMSC-derived EVs after a peroneal nerve loss of substance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>A 7\u00a0mm defect of peroneal nerve was bridged with a vein into which freshly purified or cryoconserved OEMSC-derived EVs were injected or not. These groups were compared with unoperated rats (Control) and autografted rats with the nerve sutured in inverted position (Gold Standard). Three months after surgery, nerve repair was analyzed by measuring locomotor function, muscle mechanical properties, muscle mass, axon number, and myelination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>We observed that OEMSC-derived EVs significantly (i) increased locomotor recovery, (ii) partially maintained the contractile phenotype of the target muscle, and (iii) augmented the number of growing axons. Freshly purified EVs exerted a better recovery than the Gold Standard.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>These results demonstrate that EVs display a positive effect on peripheral nerve regeneration, similarly to what has been observed with OEMSCs, the cells from which they originate. They represent an alternative to cellular therapies for peripheral nerve repair.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s13770-025-00748-3","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T10:56:58Z","timestamp":1753786618000},"page":"1227-1240","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Human Nasal Olfactory Stem Cell-Derived Extracellular Vesicles Improve the Repair of Rat Nerves"],"prefix":"10.1007","volume":"22","author":[{"given":"Maxime","family":"Bonnet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa","family":"Seblani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Witters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanguy","family":"Marqueste","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Jaloux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Morando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Decherchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"F\u00e9ron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3433-2233","authenticated-orcid":false,"given":"Ga\u00eblle","family":"Guiraudie-Capraz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"748_CR1","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1002\/dvdy.20360","volume":"233","author":"W Murrell","year":"2005","unstructured":"Murrell W, F\u00e9ron F, Wetzig A, Cameron N, Splatt K, Bellette B, et al. 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J Appl Physiol. 1985;2004:1988\u201395.","journal-title":"J Appl Physiol"}],"container-title":["Tissue Engineering and Regenerative Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13770-025-00748-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13770-025-00748-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13770-025-00748-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T05:00:13Z","timestamp":1763787613000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13770-025-00748-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,29]]},"references-count":51,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["748"],"URL":"https:\/\/doi.org\/10.1007\/s13770-025-00748-3","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.04.14.648811","asserted-by":"object"}]},"ISSN":["1738-2696","2212-5469"],"issn-type":[{"value":"1738-2696","type":"print"},{"value":"2212-5469","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,29]]},"assertion":[{"value":"1 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Experiments were performed according to the French law (Decrees and orders No. 2013-118 of 01 February 2013, JORF No. 0032) on animal care guidelines and after approval by animal Care Committees of Aix-Marseille Universit\u00e9 (AMU) and Centre National de la Recherche Scientifique (CNRS). The authorization number granted by the French Ministry of Higher Education, Research, and Innovation (MESRI) is APAFIS#41012-2023021620519181 v5, entitled \u201c\n                      R\u00e9paration du nerf p\u00e9ronier l\u00e9se avec perte de substance \u00e0 l\u2019aide d\u2019une greffe de v\u00e9sicules extracellulaires issues des cellules souches olfactives humaines, chez le rat\n                      \u201d in August 2023. All persons were licensed to conduct live animal experiments and all room have a national authorization to accommodate animals (License n\u00b0B13.013.06). Furthermore, experiments were performed in accordance with the recommendations provided in the Guide for Care and Use of Laboratory Animals (U.S. Department of Health and Human Services, National Institutes of Health), with the directives 86\/609\/EEC and 010\/63\/EU of the European Parliament and of the Council of 24 November 1986 and of 22 September 2010, respectively, and with the ARRIVE (Animal Research: Reporting of\n                      In Vivo\n                      Experiments) guidelines.  The OEMSC were collected, previously in studies involving human participants. They were reviewed and approved by Comit\u00e9 de Protection des Personnes, file 2018-A00796-49. The patients\/participants provided their written informed consent to participate in this study. Initiated in December 2018, a prospective study entitled NOSE (ClinicalTrials.gov Identifier: NCT04020367), aimed to validate the manufacture of olfactory stem cells, using good manufacturing practices, in order to use them as an Advanced Therapeutic Medicinal Product (ATMP) for repairing peripheral nerves.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}]}}