Abstract
Simple SummaryAlthough mesenchymal stem cells (MSCs) have demonstrated their therapeutic potential for osteoarthritis (OA) treatment in preclinical and clinical studies, conventional MSC-based therapies have some limitations that must be overcome. Extracellular vesicles (EVs) are bilayer membrane structures containing bioactive components including proteins, lipids, and RNAs. EVs are classified into exosomes, microvesicles, and apoptotic bodies according to sizes, origins, biomarkers, and compositions. It has been reported that MSC-derived exosomes contain a variety of cytokines, growth factors, and microRNAs, and have comparable anti-inflammatory and regenerative potentials similar to those of MSCs. Here, we review the characteristics and isolation techniques of MSC-derived exosomes and their use for the treatment of osteoarthritis (OA).Exosomes are nano-sized vesicles (50–150 nm in diameter) that contain nucleic acids (e.g., microRNA and messenger RNA), functional proteins, and bioactive lipids. They are secreted by various types of cells, including B cells, T cells, reticulocytes, dendritic cells, mast cells, epithelial cells, and mesenchymal stem cells (MSCs). They perform a wide variety of functions, including the repair of damaged tissues, regulation of immune responses, and reduction in inflammation. When considering the limitations of MSCs, including issues in standardization and immunogenicity, MSC-derived exosomes have advantages such as small dimensions, low immunogenicity, and lack of requirement for additional procedures for culture expansion or delivery. MSC-derived exosomes have shown outstanding therapeutic effects through chondro-protective and anti-inflammatory properties. MSC-derived exosomes may enable a new therapeutic paradigm for the treatment of osteoarthritis. However, further research is needed to prove their clinical effectiveness and feasibility.
Highlights
Osteoarthritis (OA) is a common pathology associated with human aging, and its pathogenesis is characterized by synovial inflammation, cartilage degradation, subchondral bone sclerosis, and osteophyte formation, which result in disability [1,2]
Exosomes are multipotent biological mediators extracted from cultured mesenchymal stem cells (MSCs)
MSC-derived exosomes have become very popular in regenerative medicine owing to their ability to repair damaged tissues
Summary
In the early inflammatory phase, innate immune cells, such as natural killer (NK) cells or macrophages, can play a significant role [5] Inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β have a catabolic function, resulting in cartilage degradation [6,7]. The levels of MSCs and favorable cytokines in the site diminish, causing their function to be restricted Through this balancing action, MSCs can be the regulation center of immune control and tissue regeneration [38]. Exosomes play a significant role in several biological processes, including intercellular communication, immune reaction and regulation, and initiation and promotion of the development and differentiation of MSCs. Exosomes are a valuable option for OA treatment. We summarize the pathophysiology and therapeutic targets of OA, and discuss EVs, especially focusing on exosomes and their therapeutic potential in OA management
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