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

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. Extracellular vesicles derived from mesenchymal stromal cells provide the therapeutic benefits of the parental cells with advantages relating to immunogenicity and ease of handling. This Review discusses the therapeutic potential of native and modified extracellular vesicles for the treatment of rheumatic diseases, focusing on osteoarthritis and rheumatoid arthritis. Extracellular vesicles (EVs) have important roles in intercellular communication and convey many components at their surface or in their cargo that reproduce the functions of parental cells.Mesenchymal stromal cell (MSC)-derived EVs can regulate and prevent symptoms in non-clinical models of osteoarthritis and rheumatoid arthritis, notably by targeting local and systemic inflammation, and restoring a healthy chondrocyte phenotype.Improvement of isolation yields of MSC-EVs and functionality optimization by pre-isolation or post-isolation engineering are still required.Clinical translation of MSC-EVs for treatment of rheumatic diseases is ongoing, suggesting future potential for the treatment of these painful and disabling diseases.