骨关节炎
软骨
间充质干细胞
微泡
再生医学
医学
关节软骨
组织工程
化学
病理
小RNA
生物医学工程
细胞
解剖
替代医学
基因
生物化学
作者
Shu Zhao,Guanghui Xiu,Jian Wang,Yi Wen,Jinyuan Lu,Baitong Wu,Guangming Wang,Danjing Yang,Bin Ling,Dajiang Du,Jun Xu
标识
DOI:10.1186/s12951-023-02086-9
摘要
Abstract Osteoarthritis (OA) is a degenerative joint disease involving cartilage. Exosomes derived from Mesenchymal stem cells (MSCs) therapy improves articular cartilage repair, but subcutaneous fat (SC) stromal cells derived exosomes (MSCs SC -Exos), especially engineering MSCs SC -Exos for drug delivery have been rarely reported in OA therapy. This objective of this study was to clarify the underlying mechanism of MSCs SC -Exos on cartilage repair and therapy of engineering MSCs SC -Exos for drug delivery in OA. MSCs SC -Exos could ameliorate the pathological severity degree of cartilage via miR-199a-3p, a novel molecular highly enriched in MSCs SC -Exos, which could mediate the mTOR-autophagy pathway in OA rat model. Intra-articular injection of antagomiR-199a-3p dramatically attenuated the protective effect of MSCs SC -Exos-mediated on articular cartilage in vivo. Furthermore, to achieve the superior therapeutic effects of MSCs SC -Exos on injured cartilage, engineering exosomes derived from MSCs SC as the chondrocyte-targeting miR-199a-3p delivery vehicles were investigated in vitro and in vivo. The chondrocyte-binding peptide (CAP) binding MSCs SC -Exos could particularly deliver miR-199a-3p into the chondrocytes in vitro and into deep articular tissues in vivo, then exert the excellent protective effect on injured cartilage in DMM-induced OA mice. As it is feasible to obtain human subcutaneous fat from healthy donors by liposuction operation in clinic, meanwhile engineering MSCs SC -Exos to realize targeted delivery of miR-199a-3p into chondrocytes exerted excellent therapeutic effects in OA animal model in vivo. Through combining MSCs SC -Exos therapy and miRNA therapy via an engineering approach, we develop an efficient MSCs SC -Exos-based strategy for OA therapy and promote the application of targeted-MSCs SC -Exos for drug delivery in the future. Graphical Abstract
科研通智能强力驱动
Strongly Powered by AbleSci AI