{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T09:15:57Z","timestamp":1783242957287,"version":"3.54.6"},"reference-count":14,"publisher":"Brieflands","issue":"1","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["brieflands.com"],"crossmark-restriction":false},"short-container-title":["Iran J Pharm Res"],"abstract":"<jats:p>Background: Corneal allograft rejection remains a leading cause of graft failure. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) may provide new options for modulating the immune response to allografts. Objectives: This study aimed to determine whether miR-146a-enriched EVs could prolong corneal allograft survival by modulating local and systemic immune responses. Methods: After corneal allografting from C57BL\/6 to BALB\/c mice, recipients received subconjunctival injections of PBS, miR-NC-EVs, or miR-146a-EVs isolated from human umbilical cord mesenchymal stem cells (hUCSCs). Local inflammatory and regulatory factors in ocular tissues were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) to quantify the expression of interleukin-1 receptor-associated kinase 1 (IRAK1), TNF receptor-associated factor 6 (TRAF6), tumor necrosis factor (TNF)-\u03b1, and forkhead box protein 3 (Foxp3). Systemic cytokine profiles were assessed in recipient sera using enzyme-linked immunosorbent assay (ELISA) to measure interferon (IFN)-\u03b3, interleukin (IL)-17, IL-10, and transforming growth factor (TGF)-\u03b2. Results: Clinical rejection scores were markedly reduced, with significant improvements in opacity, edema, and neovascularization. RT-PCR analysis of corneal tissue showed miR-146a overexpression, downregulation of IRAK1 and TRAF6, a significant reduction in TNF-\u03b1 mRNA, and increased Foxp3 expression. ELISA analysis of systemic IFN-\u03b3 and IL-17 showed that treatment with miR-146a-EVs resulted in lower systemic IFN-\u03b3 and IL-17 levels and significantly higher levels of the anti-inflammatory cytokines, IL-10 and TGF-\u03b2. Conclusions: This study identifies miR-146a-EVs as a novel cell-free therapy that effectively prolongs corneal transplant survival. The treatment exerts dual immunomodulatory effects by regulating local inflammatory pathways and shifting systemic cytokine profiles toward an anti-inflammatory state, thereby offering a targeted strategy to prevent transplant rejection.<\/jats:p>","DOI":"10.5812\/ijpr-171093","type":"journal-article","created":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T08:54:47Z","timestamp":1783241687000},"update-policy":"https:\/\/doi.org\/10.5812\/crossmark_update_policy","source":"Crossref","is-referenced-by-count":0,"title":["miR-146a-Enriched Mesenchymal Stem Cell-Derived Extracellular Vesicles Prolong Corneal Allograft Survival by Modulating Local and Systemic Immune Responses"],"prefix":"10.5812","volume":"25","author":[{"given":"Xuting","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3819","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"key-A171093REF1-1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5372090"},{"key":"key-A171093REF2-2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2015.4776"},{"key":"key-A171093REF3-3","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02313-9"},{"key":"key-A171093REF4-4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252011121"},{"key":"key-A171093REF5-5","doi-asserted-by":"publisher","DOI":"10.22037\/jcma.v8i4.41127"},{"key":"key-A171093REF6-6","doi-asserted-by":"publisher","DOI":"10.3390\/cells13020122"},{"key":"key-A171093REF7-7","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.115584"},{"key":"key-A171093REF8-8","doi-asserted-by":"publisher","DOI":"10.5812\/hepatmon-144095"},{"key":"key-A171093REF9-9","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2025.115291"},{"key":"key-A171093REF10-10","doi-asserted-by":"publisher","DOI":"10.21608\/ejvs.2024.310648.2300"},{"key":"key-A171093REF11-11","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-91291-3"},{"key":"key-A171093REF12-12","doi-asserted-by":"publisher","DOI":"10.3791\/51830"},{"key":"key-A171093REF13-13","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-03100-x"},{"key":"key-A171093REF14-14","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-042718-041717"}],"container-title":["Iranian Journal of Pharmaceutical Research"],"original-title":[],"link":[{"URL":"https:\/\/brieflands.com\/journals\/ijpr\/articles\/171093","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/brieflands.com\/journals\/ijpr\/articles\/171093","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T08:54:49Z","timestamp":1783241689000},"score":1,"resource":{"primary":{"URL":"https:\/\/brieflands.com\/journals\/ijpr\/articles\/171093"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,30]]},"references-count":14,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,5,30]]}},"alternative-id":["7ed9bac372c2e1c5e4004e4fa95a428a7fdf89fe"],"URL":"https:\/\/doi.org\/10.5812\/ijpr-171093","relation":{},"ISSN":["1726-6890"],"issn-type":[{"value":"1726-6890","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,30]]}}}