College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.
Department of Rehabilitation, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250011, China.
J Proteome Res. 2024 Apr 5;23(4):1298-1312. doi: 10.1021/acs.jproteome.3c00697. Epub 2024 Mar 18.
Our prior investigations have evidenced that bone marrow mesenchymal stem cell (BMSC) therapy can significantly improve the outcomes of rheumatoid arthritis (RA). This study aims to conduct a comprehensive analysis of the proteomics between BMSCs and BMSCs-Exos, and to further elucidate the potential therapeutic effect of BMSCs-Exos on RA, so as to establish a theoretical framework for the prevention and therapy of BMSCs-Exos on RA. The 4D label-free LC-MS/MS technique was used for comparative proteomic analysis of BMSCs and BMSCs-Exos. Collagen-induced arthritis (CIA) rat model was used to investigate the therapeutic effect of BMSCs-Exos on RA. Our results showed that some homology and differences were observed between BMSCs and BMSCs-Exos proteins, among which proteins highly enriched in BMSCs-Exos were related to extracellular matrix and extracellular adhesion. BMSCs-Exos can be taken up by chondrocytes, promoting cell proliferation and migration. In vivo results revealed that BMSCs-Exos significantly improved the clinical symptoms of RA, showing a certain repair effect on the injury of articular cartilage. In short, our study revealed, for the first time, that BMSCs-Exos possess remarkable efficacy in alleviating RA symptoms, probably through shuttling proteins related to cell adhesion and tissue repair ability in CIA rats, suggesting that BMSCs-Exos carrying expressed proteins may become a useful biomaterial for RA treatment.
我们之前的研究表明骨髓间充质干细胞（BMSC）治疗可以显著改善类风湿关节炎（RA）的疗效。本研究旨在对 BMSC 和 BMSC-Exos 之间的蛋白质组学进行全面分析，并进一步阐明 BMSC-Exos 对 RA 的潜在治疗作用，从而为 BMSC-Exos 治疗 RA 建立理论框架。我们采用 4D 无标记 LC-MS/MS 技术对 BMSC 和 BMSC-Exos 进行比较蛋白质组学分析。采用胶原诱导性关节炎（CIA）大鼠模型研究 BMSC-Exos 对 RA 的治疗作用。研究结果表明，BMSC 和 BMSC-Exos 之间存在一些同源性和差异，其中在 BMSC-Exos 中高度富集的蛋白质与细胞外基质和细胞外黏附有关。BMSC-Exos 可以被软骨细胞摄取，促进细胞增殖和迁移。体内结果表明，BMSC-Exos 显著改善了 RA 的临床症状，对关节软骨损伤具有一定的修复作用。总之，本研究首次揭示了 BMSC-Exos 在缓解 RA 症状方面具有显著疗效，可能通过在 CIA 大鼠中转运与细胞黏附和组织修复能力相关的表达蛋白来发挥作用，这提示携带表达蛋白的 BMSC-Exos 可能成为治疗 RA 的有用生物材料。
