Small extracellular vesicles from human adipose-derived stem cells attenuate cartilage degeneration
Small extracellular vesicles from human adipose-derived stem cells attenuate cartilage degeneration
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DOI：
10.1080/20013078.2020.1735249
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发表时间：
2020-01-01
影响因子：
16
通讯作者：
Cho, Yong Woo
中科院分区：
文献类型：
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作者：
Woo, Chang Hee;Kim, Hark Kyun;Cho, Yong Woo
骨关节炎（OA）是一种关节软骨的慢性退行性疾病，是世界范围内最常见的关节疾病。骨髓间充质干细胞（MSC）已被最广泛地探索用于治疗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的治疗的潜在机制。在这项研究中，我们研究了人脂肪源性干细胞EV（hASC-EV）在缓解OA中的治疗潜力，沿着其机制。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）和流式细胞术分析来表征分离的EV。hASC-EV不仅促进人OA软骨细胞的增殖和迁移，而且在体外IL-1 β存在下通过增加II型胶原合成和降低MMP-1、MMP-3、MMP-13和ADAMTS-5表达来维持软骨细胞基质。关节内注射hASC-EV显著减弱了OA进展，并在碘乙酸盐（MIA）大鼠和内侧半月板（DMM）小鼠模型的手术不稳定中保护软骨免于变性。此外，施用hASC-EV抑制M1巨噬细胞浸润到滑膜中。总体结果表明，hASC-EV应被视为治疗OA的潜在治疗方法。
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-1 beta 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.