Piñeiro-Ramil, MaríaGómez-Seoane, IvánRodríguez-Cendal, Ana IsabelSanjurjo-Rodríguez, ClaraRiva Mendoza, SelvaFuentes Boquete, Isaac ManuelDe-Toro, JavierSeñarís-Rodríguez, JoséDíaz-Prado, Silvia2025-01-282025-01-282025-01-21Piñeiro-Ramil M, Gómez-Seoane I, Rodríguez-Cendal AI, Sanjurjo-Rodríguez C, Riva-Mendoza, S, Fuentes-Boquete I, De Toro-Santos J, Señarís-Rodríguez J, Díaz-Prado S. Disease-associated signatures persist in extracellular vesicles from reprogrammed cells of osteoarthritis patients . Int J Mol Sci. 2025;26(3):870.1422-0067http://hdl.handle.net/2183/40912[Abstract] Osteoarthritis (OA) is a prevalent joint disorder that lacks effective therapies to halt cartilage degeneration. Mesenchymal stromal cell (MSC)-derived small extracellular vesicles (sEVs) are being investigated as promising chondroprotective agents. Compared to primary MSCs, induced pluripotent stem cell (iPSC)-derived MSCs (MLCs) offer superior scalability and enhanced paracrine activity. The aim of this study was to explore the feasibility of using autologous MLC-derived sEVs as a potential therapeutic strategy for OA through the analysis of their protein cargo. iPSCs from an OA patient and a healthy donor were differentiated into MLCs. sEVs were isolated from these MLCs and characterized, with a particular focus on their protein cargo. Both iPSC lines were successfully differentiated into MLCs, which secreted sEVs with comparable size distributions and yields. The analysis of differentially expressed proteins revealed a high abundance of proteins associated with OA pathology and cartilage degradation in sEVs from OA MLCs compared to those from healthy MLCs. The persistence of OA-associated protein signatures in autologous MLC-derived sEVs may limit their therapeutic efficacy. These findings underscore the importance of carefully evaluating disease-specific protein profiles in sEVs for regenerative applications.engCreative Commons Attribution 4.0 International License (CC-BY 4.0)http://creativecommons.org/licenses/by/3.0/es/Induced pluripotent stem cells (iPSCs)Mesenchymal stromal cells (MSCs)Mesenchymal-like cells (MLCs)Small extracellular vesicles (sEVs)Proteomic analysisCartilage degradationRegenerative medicineAutologous cell therapyjournal articleopen access10.3390/ijms26030870