ABSTRACT

Osteoarthritis (OA) is a chronic degenerative disease of articular cartilage that is the most common joint disease worldwide. Mesenchymal stem cells (MSCs) have been the most extensively explored for the treatment of OA. Recently, it has been demonstrated that MSC-derived extracellular vesicles (EVs) may contribute to the potential mechanisms of MSC-based therapies. In this study, we investigated the therapeutic potential of human adipose-derived stem cells EVs (hASC-EVs) in alleviating OA, along with the mechanism. EVs were isolated from the culture supernatants of hASCs by a multi-filtration system based on the tangential flow filtration (TFF) system. The isolated EVs were characterised using dynamic light scattering (DLS), transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and flow cytometry analysis. The hASC-EVs not only promoted the proliferation and migration of human OA chondrocytes, but also maintained the chondrocyte matrix by increasing type Ⅱ collagen synthesis and decreasing MMP-1, MMP-3, MMP-13 and ADAMTS-5 expression in the presence of IL-1β in vitro. Intra-articular injection of hASC-EVs significantly attenuated OA progression and protected cartilage from degeneration in both the monosodium iodoacetate (MIA) rat and the surgical destabilisation of the medial meniscus (DMM) mouse models. In addition, administration of hASC-EVs inhibited the infiltration of M1 macrophages into the synovium. Overall results suggest that the hASC-EVs should be considered as a potential therapeutic approach in the treatment of OA.

摘要

骨关节炎（OA）是一种关节软骨的慢性退行性疾病，是全球最常见的关节疾病。间充质干细胞（MSCs）已被最广泛地用于治疗OA。最近，已经证明，MSC衍生的细胞外囊泡（EV）可能有助于基于MSC的疗法的潜在机制。在这项研究中，我们研究了人类脂肪干细胞电动车（hASC-EV）在缓解OA中的治疗潜力及其机理。通过基于切向流过滤（TFF）系统的多重过滤系统，从hASC的培养上清液中分离出EV。使用动态光散射（DLS），透射电子显微镜（TEM），纳米颗粒跟踪分析（NTA）和流式细胞仪分析对分离出的电动汽车进行表征。体外。关节内注射hASC-EVs可以显着减缓OA进展，并保护软骨免受碘乙酸单钠（MIA）大鼠和内侧半月板（DMM）小鼠模型的手术不稳定的影响。另外，施用hASC-EV抑制了M1巨噬细胞向滑膜的浸润。总体结果表明，应将hASC-EV视为治疗OA的潜在治疗方法。