间充质干细胞来源外泌体在膝骨关节炎微环境中的作用

The Role of Mesenchymal Stem Cell-derived Exosomes in Microenvironment of Knee Osteoarthritis

骨关节炎是一种涉及所有关节成分(包括关节软骨、软骨下骨、滑膜、韧带、关节囊和关节周围肌肉)的关节退行性疾病,会导致严重的残疾,其中最常见的是膝骨关节炎(knee osteoarthritis,KOA)。外泌体是一种由不同细胞分泌的直径为40~100 nm的胞外囊泡,可以传递DNA、微小RNA、m RNA、蛋白质等多种物质,并通过多种方式进行细胞间的信息传递和功能调节。间充质干细胞(mesenchymal stem cells,MSCs)可以从骨髓、脂肪、滑膜及外周血等组织分离,是一类具有多向分化潜能的祖细胞,以干细胞为基础的疗法可以修复软骨损伤,对抗KOA的发展,间充质干细胞能够分泌多种营养因子来调节受损的微环境,其中间充质干细胞来源的外泌体被认为在KOA炎症反应及软骨细胞代谢中发挥着重要的作用,其能够调节膝骨关节微环境中B细胞、T细胞、滑膜细胞、软骨细胞代谢及其细胞外基质的分解与合成平衡,维持软骨稳态。近期有多项研究表明,不同组织来源的间充质干细胞外泌体对骨关节炎均有明确的治疗作用,本文就MSCs来源的外泌体治疗KOA的具体机制进行综述,以期对干细胞治疗KOA提供理论依据。

Osteoarthritis is a degenerative disease of the joints, which involves all components of joints including articular cartilage, subchondral bone, synovium, ligaments, joint capsule, and muscles around the joints. It can lead to severe disability, the most common of which is knee osteoarthritis(KOA). Exosomes are extracellular vesicles with a diameter of 40-100 nm secreted by different cells, which can transmit DNA, micro RNA, m RNA, protein and other substances, and carry out intercellular information transmission and function regulation in a variety of ways. Mesenchymal stem cells(MSCs) can be isolated from bone marrow, fat, synovium, peripheral blood and other tissues, and are a kind of progenitor cells with multi-direction differentiation potential. Stembased therapies can repair cartilage damage and combat the development of KOA. Mesenchymal stem cells can secrete a variety of nutritional factors to regulate the damaged microenvironment, among which exosomes derived from mesenchymal stem cells are believed to play an important role in the inflammatory response and chondrocyte metabolism of KOA. It can regulate the metabolism of B cells, T cells, synovial cells, chondrocytes and the decomposition and synthesis balance of extracellular matrix in the knee joint microenvironment, and maintain cartilage homeostasis. A number of recent studies have shown that exosomes derived from mesenchymal stem cells from different tissues have definite therapeutic effects on osteoarthritis. This paper reviews the specific mechanism of exosomes derived from MSCs in the treatment of KOA, in order to provide theoretical basis for stem cell treatment of KOA.