{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T16:10:35Z","timestamp":1791648635345,"version":"4.3.4"},"reference-count":110,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T00:00:00Z","timestamp":1712620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"International Institute of Translational Medicine, Poland"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Corneal ulcers, characterized by severe inflammation of the cornea, can lead to serious, debilitating complications and may be vision-threatening for horses. In this study, we aimed to investigate the role of endoplasmic reticulum (ER) stress in corneal stem progenitor cell (CSSC) dysfunction and explore the potential of equine adipose-derived stromal stem cell (ASC)-derived extracellular vesicles (EVs) to improve corneal wound healing. We showed that CSSCs expressed high levels of CD44, CD45, and CD90 surface markers, indicating their stemness. Supplementation of the ER-stress-inducer tunicamycin to CSSCs resulted in reduced proliferative and migratory potential, accumulation of endoplasmic reticulum (ER)-stressed cells in the G0\/G1 phase of the cell cycle, increased expression of proinflammatory genes, induced oxidative stress and sustained ER stress, and unfolded protein response (UPR). Importantly, treatment with EVs increased the proliferative activity and number of cells in the G2\/Mitosis phase, enhanced migratory ability, suppressed the overexpression of proinflammatory cytokines, and upregulated the anti-inflammatory miRNA-146a-5p, compared to control and\/or ER-stressed cells. Additionally, EVs lowered the expression of ER-stress master regulators and effectors (PERK, IRE1, ATF6, and XBP1), increased the number of mitochondria, and reduced the expression of Fis-1 and Parkin, thereby promoting metabolic homeostasis and protecting against apoptosis in equine CSSCs. Our findings demonstrate that MSCs-derived EVs represent an innovative and promising therapeutic strategy for the transfer of bioactive mediators which regulate various cellular and molecular signaling pathways.<\/jats:p>","DOI":"10.3390\/cimb46040204","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T10:08:50Z","timestamp":1712657330000},"page":"3251-3277","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Extracellular Vesicles Isolated from Equine Adipose-Derived Stromal Stem Cells (ASCs) Mitigate Tunicamycin-Induced ER Stress in Equine Corneal Stromal Stem Cells (CSSCs)"],"prefix":"10.3390","volume":"46","author":[{"given":"Justyna M.","family":"Meissner","sequence":"first","affiliation":[{"name":"Department of Experimental Biology, Faculty of Biology and Animal Science, Wroc\u0142aw University of Environmental and Life Sciences, Norwida 27B, 50-375 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7257-6741","authenticated-orcid":false,"given":"Aleksandra","family":"Chmieli\u0144ska","sequence":"additional","affiliation":[{"name":"International Institute of Translational Medicine, Jesionowa 11, Malin, 55-114 Wisznia Mala, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3825-3113","authenticated-orcid":false,"given":"Ron","family":"Ofri","sequence":"additional","affiliation":[{"name":"Koret School of Veterinary Medicine, Hebrew University of Jerusalem, P.O. Box 12, Rehovot 7610001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Cis\u0142o-Sankowska","sequence":"additional","affiliation":[{"name":"International Institute of Translational Medicine, Jesionowa 11, Malin, 55-114 Wisznia Mala, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Marycz","sequence":"additional","affiliation":[{"name":"Department of Experimental Biology, Faculty of Biology and Animal Science, Wroc\u0142aw University of Environmental and Life Sciences, Norwida 27B, 50-375 Wroclaw, Poland"},{"name":"International Institute of Translational Medicine, Jesionowa 11, Malin, 55-114 Wisznia Mala, Poland"},{"name":"Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95516, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,9]]},"reference":[{"key":"ref_1","first-page":"E4","article-title":"Corneal Ulcers in Horses","volume":"35","author":"Williams","year":"2013","journal-title":"Compend. 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