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间充质基质细胞衍生细胞外囊泡在风湿性疾病中的治疗潜力。

Therapeutic potential in rheumatic diseases of extracellular vesicles derived from mesenchymal stromal cells.

机构信息

IRMB, University of Montpellier, INSERM, 34295, Montpellier, France.

Clinical Immunology and Osteoarticular Disease Therapeutic Unit, Department of Rheumatology, CHU Montpellier, 34095, Montpellier, France.

出版信息

Nat Rev Rheumatol. 2023 Nov;19(11):682-694. doi: 10.1038/s41584-023-01010-7. Epub 2023 Sep 4.

Abstract

The incidence of rheumatic diseases such as rheumatoid arthritis and osteoarthritis and injuries to articular cartilage that lead to osteochondral defects is predicted to rise as a result of population ageing and the increase in high-intensity physical activities among young and middle-aged people. Current treatments focus on the management of pain and joint functionality to improve the patient's quality of life, but curative strategies are greatly desired. In the past two decades, the therapeutic value of mesenchymal stromal cells (MSCs) has been evaluated because of their regenerative potential, which is mainly attributed to the secretion of paracrine factors. Many of these factors are enclosed in extracellular vesicles (EVs) that reproduce the main functions of parental cells. MSC-derived EVs have anti-inflammatory, anti-apoptotic as well as pro-regenerative activities. Research on EVs has gained considerable attention as they are a potential cell-free therapy with lower immunogenicity and easier management than whole cells. MSC-derived EVs can rescue the pathogenetic phenotypes of chondrocytes and exert a protective effect in animal models of rheumatic disease. To facilitate the therapeutic use of EVs, appropriate cell sources for the production of EVs with the desired biological effects in each disease should be identified. Production and isolation of EVs should be optimized, and pre-isolation and post-isolation modifications should be considered to maximize the disease-modifying potential of the EVs.

摘要

由于人口老龄化以及年轻人和中年人高强度体育活动的增加,预计类风湿性关节炎和骨关节炎等风湿性疾病以及导致骨软骨缺损的关节软骨损伤的发病率将会上升。目前的治疗方法侧重于管理疼痛和关节功能,以提高患者的生活质量,但人们非常希望有更有效的治疗策略。在过去的二十年中,间充质基质细胞(MSCs)的治疗价值得到了评估,因为它们具有再生潜力,这主要归因于旁分泌因子的分泌。这些因子中的许多都包含在细胞外囊泡(EVs)中,EVs 复制了亲本细胞的主要功能。MSC 衍生的 EVs 具有抗炎、抗凋亡和促再生作用。由于 EVs 作为一种潜在的无细胞治疗方法,其免疫原性比全细胞更低,且更容易管理,因此引起了相当大的关注。MSC 衍生的 EVs 可以挽救软骨细胞的致病表型,并在风湿性疾病的动物模型中发挥保护作用。为了促进 EVs 的治疗应用,应该确定合适的细胞来源,以在每种疾病中产生具有所需生物学效应的 EVs。应优化 EVs 的生产和分离,并考虑预分离和后分离的修饰,以最大限度地提高 EVs 的疾病修饰潜力。

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