Li Haobo, Xiang Dong, Gong Chongcheng, Wang Xiaomin, Liu Lin
Department of Orthopaedics and Traumatology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Orthopaedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China.
Front Bioeng Biotechnol. 2023 Jan 4;10:1109074. doi: 10.3389/fbioe.2022.1109074. eCollection 2022.
Intra-articular injection of adipose mesenchymal stem cells (ADSCs) is a potential alternative to the treatment of osteoarthritis (OA) and has aroused great interest of clinical researchers. However, the hostile microenvironment in the joint cavity, characterized by reactive oxygen species (ROS) accumulation and excessive inflammation, disturbs the bioactivity of the transplanted stem cells. The (-)-epigallocatechin-3-O-gallate (EGCG), a green tea catechin, has attracted the researchers' attention owing to its powerful ROS-scavenging and antioxidant properties. In this study, to avoid rapid degradation and/or depletion of EGCG, we prepare a long-lasting injectable hydrogel by EGCG and hyaluronic acid (HA). The naturally derived hydrogels with excellent biocompatibility and durable retention time can capture the redundant ROS continuously and efficiently, thus protecting ADSCs from ROS-mediated death and bioactivity inhibition, including cell survival, proliferation and chondrogenic differentiation. Intra-articular injection of this ADSCs loaded hydrogel significantly induced synovial macrophages polarization to M2 phenotype, decreased pro-inflammatory cytokines (e.g., IL-1β, MMP-13, and TNF-α) expression, promoted cartilage matrix formation, and repaired cartilage destruction in OA. This stem cell-protected hydrogel delivery strategy showed superior efficacy than ADSCs delivering or EGCG-HA injection singly, which providing a potential alternative strategy for OA management.
关节腔内注射脂肪间充质干细胞（ADSCs）是治疗骨关节炎（OA）的一种潜在替代方法，已引起临床研究人员的极大兴趣。然而，关节腔内以活性氧（ROS）积累和过度炎症为特征的恶劣微环境会干扰移植干细胞的生物活性。（-）-表没食子儿茶素-3-O-没食子酸酯（EGCG）是一种绿茶儿茶素，因其强大的ROS清除和抗氧化特性而引起了研究人员的关注。在本研究中，为避免EGCG快速降解和/或耗尽，我们用EGCG和透明质酸（HA）制备了一种长效可注射水凝胶。这种具有优异生物相容性和持久保留时间的天然衍生水凝胶可以持续有效地捕获多余的ROS，从而保护ADSCs免受ROS介导的死亡和生物活性抑制，包括细胞存活、增殖和软骨形成分化。关节腔内注射这种负载ADSCs的水凝胶可显著诱导滑膜巨噬细胞极化为M2表型，降低促炎细胞因子（如IL-1β、MMP-13和TNF-α）的表达，促进软骨基质形成，并修复OA中的软骨破坏。这种干细胞保护水凝胶递送策略显示出比单独递送ADSCs或注射EGCG-HA更高的疗效，为OA管理提供了一种潜在的替代策略。
