Intra-articular injection of (MSCs) significantly alleviates pain and improves joint function in knee osteoarthritis (KOA).
Mesenchymal stem cells and their (MSC-EVs) are associated with anti-inflammatory and regenerative effects beneficial for knee osteoarthritis.
Clinical studies demonstrate a favorable safety profile for MSC injections in the treatment of KOA.
MSC-EVs reduce joint inflammation by modulating immune cell behavior and inhibiting inflammatory pathways.
These extracellular vesicles help maintain cartilage structure by promoting the production of cartilage-related proteins and inhibiting enzymes that break down cartilage.
MSC-EVs are linked to increased chondrocyte survival and function, potentially aiding in cartilage repair.
Advancements in engineered MSC-EVs aim to enhance targeted delivery of therapeutic agents to chondrocytes, potentially improving treatment outcomes for KOA.
Simplified
Knee osteoarthritis (KOA) is a prevalent degenerative joint disease characterized by progressive articular cartilage degeneration, synovial inflammation, and abnormal subchondral bone remodeling, with no curative treatment currently available. (MSCs) and their (MSC-EVs) have emerged as promising therapeutic strategies for KOA due to their anti-inflammatory, regenerative, and immunomodulatory properties. Clinical studies demonstrate that intra-articular MSCs injection significantly alleviates pain, improves joint function, and exhibits a favorable safety profile. MSC-EVs show enhanced therapeutic potential owing to their low immunogenicity, high stability, and targeted delivery capabilities. This review systematically examines the therapeutic role of MSCs and MSC-EVs in KOA treatment. Mechanistic studies reveal that MSC-EVs ameliorate joint inflammatory microenvironments by regulating macrophage polarization, inhibiting key inflammatory pathways (NF-κB, MAPK), and suppressing pro-inflammatory cytokine release (IL-1β, TNF-α). Furthermore, MSC-EVs protect extracellular matrix integrity and promote cartilage regeneration by upregulating chondrogenic markers (Sox9, aggrecan, type II collagen) while downregulating matrix-degrading enzymes (MMP-13, ADAMTS5). Additionally, MSC-EVs enhance chondrocyte proliferation and migration while inhibiting apoptosis and senescence, potentially through activation of YAP and JAK/STAT signaling pathways. These multifaceted mechanisms collectively facilitate cartilage repair and regeneration. Advances in engineered EVs technology and novel delivery systems provide strategies to further enhance MSC-EVs efficacy. Engineered EVs modified with chondrocyte-targeting peptides or loaded with therapeutic molecules (drugs, miRNAs, siRNAs) can deliver bioactive compounds to specific sites and precisely regulate chondrocyte function, thereby alleviating KOA symptoms. This review comprehensively examines the clinical efficacy and underlying mechanisms of MSCs and MSC-EVs in KOA treatment, discusses current clinical application challenges, and outlines future research directions for advancing precision therapeutic strategies.
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