Engineering exosomes derived from subcutaneous fat MSCs specially promote cartilage repair as miR-199a-3p delivery vehicles in Osteoarthritis

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
出处
期刊:Journal of Nanobiotechnology [Springer Nature]
卷期号:21 (1) 被引量:24
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
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