Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Department of Orthopaedics, Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China.
J Nanobiotechnology. 2024 Jun 19;22(1):345. doi: 10.1186/s12951-024-02632-z.
Osteoarthritis (OA) is a common degenerative joint disease which currently lacks of effective agents. It is therefore urgent and necessary to seek an effective approach that can inhibit inflammation and promote cartilage matrix homeostasis. Cartilage progenitor cells (CPCs) are identified as a cell population of superficial zone in articular cartilage which possess strong migration ability, proliferative capacity, and chondrogenic potential. Recently, the application of CPCs may represent a novel cell therapy strategy for OA treatment. There is growing evidence that extracellular vesicles (EVs) are primary mediators of the benefits of stem cell-based therapy. In this study, we explored the protective effects of CPCs-derived EVs (CPCs-EVs) on IL-1β-induced chondrocytes. We found CPCs-EVs exhibited chondro-protective effects in vitro. Furthermore, our study demonstrated that CPCs-EVs promoted matrix anabolism and inhibited inflammatory response at least partially via blocking STAT3 activation. In addition, liquid chromatography-tandem mass spectrometry analysis identified 991 proteins encapsulated in CPCs-EVs. By bioinformatics analysis, we showed that STAT3 regulatory proteins were enriched in CPCs-EVs and could be transported to chondrocytes. To promoting the protective function of CPCs-EVs in vivo, CPCs-EVs were modified with cationic peptide ε-polylysine-polyethylene-distearyl phosphatidylethanolamine (PPD) for surface charge reverse. In posttraumatic OA mice, our results showed PPD modified CPCs-EVs (PPD-EVs) effectively inhibited extracellular matrix catabolism and attenuated cartilage degeneration. Moreover, PPD-EVs down-regulated inflammatory factors expressions and reduced OA-related pain in OA mice. In ex-vivo cultured OA cartilage explants, PPD-EVs successfully promoted matrix anabolism and inhibited inflammation. Collectively, CPCs-EVs-based cell-free therapy is a promising strategy for OA treatment.
骨关节炎（OA）是一种常见的退行性关节疾病，目前缺乏有效的治疗方法。因此，迫切需要寻求一种有效的方法来抑制炎症和促进软骨基质的动态平衡。软骨祖细胞（CPCs）被鉴定为关节软骨浅表层的一种细胞群，具有很强的迁移能力、增殖能力和软骨生成潜力。最近，CPCs 的应用可能代表了 OA 治疗的一种新的细胞治疗策略。越来越多的证据表明，细胞外囊泡（EVs）是基于干细胞的治疗益处的主要介质。在本研究中，我们探讨了 CPCs 衍生的 EVs（CPCs-EVs）对 IL-1β诱导的软骨细胞的保护作用。我们发现 CPCs-EVs 在体外具有软骨保护作用。此外，我们的研究表明，CPCs-EVs 通过阻断 STAT3 激活，至少部分促进了基质合成代谢和抑制炎症反应。此外，液相色谱-串联质谱分析鉴定了 991 种包裹在 CPCs-EVs 中的蛋白质。通过生物信息学分析，我们表明 STAT3 调节蛋白在 CPCs-EVs 中富集，并可被转运到软骨细胞中。为了促进 CPCs-EVs 在体内的保护作用，我们用阳离子肽 ε-聚赖氨酸-聚乙二醇-二硬脂酰基磷脂酰乙醇胺（PPD）对 CPCs-EVs 进行表面电荷反转修饰。在创伤后 OA 小鼠中，我们的结果表明，PPD 修饰的 CPCs-EVs（PPD-EVs）能有效抑制细胞外基质的分解代谢，减轻软骨退变。此外，PPD-EVs 下调了 OA 小鼠的炎症因子表达，减轻了 OA 相关疼痛。在体外培养的 OA 软骨标本中，PPD-EVs 成功促进了基质合成代谢和抑制了炎症。总之，基于 CPCs-EVs 的无细胞治疗是 OA 治疗的一种有前途的策略。
