168596 20260211123813.0 doi 10.3390/pharmaceutics18020193 sideral 147954 ART-2026-147954 eng Marco-Brualla, Joaquín The Combination of Immunomodulatory Secretome and Liposome-Bound TRAIL Improves Knee Osteoarthritis Symptoms in an Ovine Model 2026 Background/Objectives: Knee osteoarthritis stands as the highest prevalent joint disease worldwide, affecting millions of adults and significantly impairing mobility and quality of life. Pro-inflammatory cells and cytokines are considered key players in the pathophysiology of the disease. In previous work, two anti-inflammatory therapeutic approaches were developed: a secretome enriched in anti-inflammatory cytokines, and nanoliposome-bound TRAIL (LUV-TRAIL), with proven efficacy against rheumatoid arthritis in rabbits. Methods: In this work, we evaluated the ability of these treatments to prevent the development of osteoarthritis (OA) in an ovine model following meniscectomies. Two weeks after the surgeries, knees were treated with several rounds of single or combined therapy, and then sheep were left untreated for several months. Knee damage was followed by X-ray analysis and, after sacrifice, assessed through macroscopic inspection, histological determinations, and inflammatory cytokine measurements. Results: The combined therapy had a significant positive effect against osteoarthritis development. Specifically, the combination is capable of improving knee injury in the first stages of OA in several parameters, such as synovial hyperplasia and tibial plateau damage, which are two of the most frequently damaged areas. Other markers, such as synovial inflammation and X-ray and macroscopic images, also presented a tendency to improved scores. Conclusions: The combination of the secretome with LUV-TRAIL represents a promising therapy worth exploring further in osteoarthritis treatment and/or prevention. Access copy available to the general public Unrestricted info:eu-repo/grantAgreement/ES/DGA/B31-20R info:eu-repo/grantAgreement/ES/DGA/B23-20R info:eu-repo/grantAgreement/ES/UZ/OTRI-2022-0396 info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion García-Álvarez, Felícito Fuente, Sara Universidad de Zaragoza Fernández, Pablo Vitoria, Arantza Universidad de Zaragoza (orcid)0000-0003-1286-4968 Vázquez, Francisco José Universidad de Zaragoza (orcid)0000-0002-8712-2275 Lapuente-Fernández, Juan Pedro Martínez-Lostao, Luis Universidad de Zaragoza (orcid)0000-0003-3043-147X Romero, Antonio Universidad de Zaragoza (orcid)0000-0001-7188-0461 Anel, Alberto Universidad de Zaragoza (orcid)0000-0002-5175-8394 1011 566 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Inmunología 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 1009 617 Universidad de Zaragoza Dpto. Patología Animal Área Medicina y Cirugía Animal 18, 2 (2026), 193 [21 pp.] Pharmaceutics Pharmaceutics 1999-4923 4730495 http://zaguan.unizar.es/record/168596/files/texto_completo.pdf Versión publicada 2441555 http://zaguan.unizar.es/record/168596/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:168596 articulos driver 2026-02-11-10:27:56 ARTICLE