Chen Manyu, Liu Yuhan, Cao Yi, Zhao Chengkun, Liu Quanying, Li Na, Liu Yuan, Cui Xiaolin, Liu Pengcheng, Liang Jie, Fan Yujiang, Wang Qiguang, Zhang Xingdong
National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, 29 Wangjiang Road, Chengdu 610064, P. R. China.
The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, China.
ACS Nano. 2025 Feb 4;19(4):4924-4941. doi: 10.1021/acsnano.4c16785. Epub 2025 Jan 23.
Osteoarthritis (OA) presents a significant therapeutic challenge, with few options for preserving joint cartilage and repairing associated tissue damage. Inflammation is a pivotal factor in OA-induced cartilage deterioration and synovial inflammation. Recently, exosomes derived from human umbilical cord mesenchymal stem cells (HucMSCs) have gained recognition as a promising noncellular therapeutic modality, but their use is hindered by the challenge of harvesting a sufficient number of exosomes with effective therapeutic efficacy. Given that HucMSCs are highly sensitive to microenvironmental signals, we hypothesized that priming HucMSCs within a proinflammatory environment would increase the number of exosomes secreted with enhanced anti-inflammatory properties. Subsequent miRNA profiling and pathway analysis confirmed that interleukin-1 beta (IL-1β)-induced exosomes (C-Exos) exert positive effects through miRNA regulation and signaling pathway modulation. experiments revealed that C-Exos enhance chondrocyte functionality and cartilage matrix production, as well as macrophage polarization, thereby enhancing cartilage repair. C-Exos were encapsulated in hyaluronic acid hydrogel microspheres (HMs) to ensure sustained release, leading to substantial improvements in the inflammatory microenvironment and cartilage regeneration in a rat OA model. This study outlines a strategy to tailor exosome cargo for anti-inflammatory and cartilage regenerative purposes, with the functionalized HMs demonstrating potential for OA treatment.
骨关节炎（OA）带来了重大的治疗挑战，在保留关节软骨和修复相关组织损伤方面选择有限。炎症是OA诱导的软骨退化和滑膜炎症的关键因素。最近，源自人脐带间充质干细胞（HucMSCs）的外泌体已被公认为一种有前景的非细胞治疗方式，但其应用受到获取足够数量具有有效治疗效果的外泌体这一挑战的阻碍。鉴于HucMSCs对微环境信号高度敏感，我们假设在促炎环境中预处理HucMSCs会增加分泌的具有增强抗炎特性的外泌体数量。随后的miRNA谱分析和通路分析证实，白细胞介素-1β（IL-1β）诱导的外泌体（C-Exos）通过miRNA调节和信号通路调节发挥积极作用。实验表明，C-Exos可增强软骨细胞功能和软骨基质产生，以及巨噬细胞极化，从而促进软骨修复。将C-Exos封装在透明质酸水凝胶微球（HMs）中以确保持续释放，在大鼠OA模型中导致炎症微环境和软骨再生得到显著改善。本研究概述了一种为抗炎和软骨再生目的定制外泌体货物的策略，功能化的HMs显示出治疗OA的潜力。
