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Effective management therefore requires both accurate diagnosis and treatment of these primary causes and the implementation of strategies to promote tissue repair and regeneration. While an acute wound typically heals within 4\u20136 weeks through orderly phases of hemostasis, inflammation, proliferation, and remodeling, a chronic wound remains unresolved beyond this period, often due to prolonged inflammation or disruption of one or more healing stages. This study evaluated the therapeutic efficacy of WJ-MSC-derived EVs in adult cats with chronic ulcers persisting for more than four weeks. These EVs support essential biological processes, including immune modulation, tissue regeneration, cellular homeostasis, anti-inflammatory actions, and anti-fibrotic activity. Twenty cats were divided into two groups: an EV-treated group receiving carboxymethyl cellulose (CMC) gel loaded loaded with Wharton's Jelly mesenchymal stem cell-derived extracellular vesicles (WJ-MSC-derived EVs) (100 \u03bcg EV protein\/cm\n                    <jats:sup>2<\/jats:sup>\n                    wound area) alongside standard care, and a control group receiving CMC gel (in house prepared 2% concentration) alone. EV treatment significantly accelerated ulcer healing, with markedly enhanced wound contraction and near-complete closure by Day 16 (92.4\u2009\u00b1\u20096.8%) compared with controls (58.3\u2009\u00b1\u200912.1% at Day 16). Histopathology revealed superior epithelialization, earlier collagen deposition, and better connective tissue organization in EV-treated wounds. Immunohistochemistry demonstrated increased \u03b1-SMA and CD31 expression, indicating active angiogenesis and tissue remodeling. Additionally, scratch assays showed improved cellular migration in response to EVs. Overall, In this pilot study of client-owned cats, WJ-MSC-derived EVs demonstrated beneficial effects on wound healing, with significantly accelerated contraction and improved histological organization compared to standard care alone. However, due to the small sample size, etiological and therapeutic heterogeneity, and study design limitations, external validity remains limited. These findings suggest WJ-MSC-derived EVs may represent a promising adjunctive therapy for feline chronic ulcers, but larger, etiology-stratified trials are needed before recommending this as an established alternative treatment. Further research should focus on standardizing treatment protocols, identifying optimal patient selection criteria, and evaluating long-term outcomes.\n                  <\/jats:p>","DOI":"10.1186\/s13620-026-00341-7","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T04:14:57Z","timestamp":1776140097000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Healing the unhealable: Wharton's jelly stem cell vesicles as a breakthrough for feline chronic skin ulcers"],"prefix":"10.1186","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2314-8820","authenticated-orcid":false,"given":"Mohamed S.","family":"kishta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salem A.","family":"Serag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed N.","family":"Abdallah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed M.","family":"Bahr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf A.","family":"Shamaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdallah M.","family":"Hafez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basma","family":"Salah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"341_CR1","doi-asserted-by":"publisher","unstructured":"\u00d6zayd\u0131n \u0130, Ayd\u0131n U. 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Wound Repair Regen. 2013;21(3):372\u201381.","journal-title":"Wound Repair Regen"},{"issue":"4","key":"341_CR51","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/j.cvsm.2006.03.002","volume":"36","author":"BG Campbell","year":"2006","unstructured":"Campbell BG. Dressings, bandages, and splints for wound management in dogs and cats. Vet Clin North Am Small Anim Pract. 2006;36(4):759\u201391.","journal-title":"Vet Clin North Am Small Anim Pract"},{"issue":"1","key":"341_CR52","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1007\/s10876-022-02224-7","volume":"34","author":"AA Abd-Rabou","year":"2023","unstructured":"Abd-Rabou AA, Ahmed HH, Kishta MS, Zoheir KM. Selective viramidine-loaded aptamer-nanoparticles trigger cell cycle arrest in nucleolin-expressed hepatoma cells through modulation of CDC25A\/p53\/PI3k pathway. 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Vet Dermatol. 2022;33(1):91-e27.","journal-title":"Vet Dermatol"}],"container-title":["Irish Veterinary Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13620-026-00341-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13620-026-00341-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13620-026-00341-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T21:58:33Z","timestamp":1781647113000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13620-026-00341-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,14]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["341"],"URL":"https:\/\/doi.org\/10.1186\/s13620-026-00341-7","relation":{},"ISSN":["2046-0481"],"issn-type":[{"value":"2046-0481","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,14]]},"assertion":[{"value":"2 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study \u201c\n                      The transformative potential of Wharton Jelly mesenchymal stem cell-derived extracellular vesicles for clinically non\u2013healing skin wound and ulcer\n                      \u201d was ethically approved by the ethical committee of the Kafr El-Sheikh University (Approval number: KFS-IACUC\/207\/2024). Written informed consent for participation and publication of experimental results was obtained from the animal\u2019s owners involved in this study. All authors consented their participation and agreed on publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors consented their participation and agreed on publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"24"}}