Piñeiro-Ramil María, Gómez-Seoane Iván, Rodríguez-Cendal Ana Isabel, Sanjurjo-Rodríguez Clara, Riva-Mendoza Selva, Fuentes-Boquete Isaac, De Toro-Santos Javier, Señarís-Rodríguez José, Díaz-Prado Silvia
Grupo de Investigación en Terapia Celular y Medicina Regenerativa, Instituto de Investigación Biomédica de A Coruña (INIBIC), Fundación Pública Gallega de Investigación Biomédica INIBIC, Complexo Hospitalario Universitario de A Coruña (CHUAC), Servizo Galego de Saúde (SERGAS), 15006 A Coruña, Spain.
Grupo de Investigación en Terapia Celular y Medicina Regenerativa, Departamento de Fisioterapia, Medicina y Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidade da Coruña (UDC), 15006 A Coruña, Spain.
Int J Mol Sci. 2025 Jan 21;26(3):870. doi: 10.3390/ijms26030870.
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.
骨关节炎（OA）是一种常见的关节疾病，缺乏有效的治疗方法来阻止软骨退变。间充质基质细胞（MSC）衍生的小细胞外囊泡（sEV）正作为有前景的软骨保护剂进行研究。与原代MSC相比，诱导多能干细胞（iPSC）衍生的MSC（MLC）具有更好的可扩展性和增强的旁分泌活性。本研究的目的是通过分析其蛋白质负载，探讨使用自体MLC衍生的sEV作为OA潜在治疗策略的可行性。从一名OA患者和一名健康供体的iPSC分化为MLC。从这些MLC中分离并鉴定sEV，特别关注其蛋白质负载。两条iPSC系均成功分化为MLC，它们分泌的sEV具有相似的大小分布和产量。差异表达蛋白质分析显示，与健康MLC来源的sEV相比，OA MLC来源的sEV中与OA病理和软骨降解相关的蛋白质丰度很高。自体MLC衍生的sEV中OA相关蛋白质特征的持续存在可能会限制其治疗效果。这些发现强调了在再生应用中仔细评估sEV中疾病特异性蛋白质谱的重要性。
