Mesenchymal stem cells (MSCs) are being explored as a promising therapeutic strategy for rheumatoid arthritis (RA) due to their immunosuppressive and tissue-regenerating properties. Traditional RA treatments, such as glucocorticoids, NSAIDs, DMARDs, and TNF inhibitors, often have limited efficacy and significant side effects, including myelosuppression, organ damage, and increased cancer risk. MSCs, with their low immunogenicity and ability to home to inflamed tissues, offer a more targeted and effective approach. They can suppress inflammation by modulating immune cells, secreting anti-inflammatory cytokines like TGF-β1, PGE-2, and IL-10, and releasing extracellular vesicles that regulate immune responses. MSCs also promote tissue repair by differentiating into osteoblasts and chondrocytes, aiding in the regeneration of damaged joint tissues. MSCs inhibit pro-inflammatory cytokines such as TNF-α and IL-1β, which are central to RA pathogenesis. They reduce the activity of effector T cells, promote regulatory T cells (Tregs), and inhibit the differentiation of harmful T helper cells (Th17). MSCs also modulate macrophage polarization, shifting them from pro-inflammatory M1 to anti-inflammatory M2 types, which helps reduce joint inflammation. Additionally, MSCs can inhibit B cell proliferation and antibody production, which are key factors in RA progression. The effectiveness of MSCs is enhanced by appropriate inflammatory signals, such as IFN-γ, which improve their immunosuppressive capacity. However, excessive inflammation can impair MSC function, highlighting the need for strategies to optimize the inflammatory microenvironment. MSCs also promote the production of anti-inflammatory cytokines like IL-10 and TGF-β, which help regulate immune responses and reduce joint damage. They can be engineered to express specific molecules, such as CXCR7, to enhance their homing and therapeutic effects. MSCs have been shown to reduce bone erosion and cartilage destruction by inhibiting osteoclast formation and promoting osteoblast differentiation. They also secrete factors that inhibit matrix metalloproteinases (MMPs), which are involved in cartilage and bone degradation. Despite their potential, challenges remain in the clinical application of MSCs for RA, including ensuring their survival and function in the inflammatory joint environment. Strategies such as using hydrogels to deliver MSCs directly to the joint, combining MSCs with antioxidants or other therapeutic agents, and genetic modification to enhance homing and survival are being explored. Overall, MSCs offer a promising approach for RA therapy by combining immunomodulation and tissue regeneration, with ongoing research aimed at improving their efficacy and safety.Mesenchymal stem cells (MSCs) are being explored as a promising therapeutic strategy for rheumatoid arthritis (RA) due to their immunosuppressive and tissue-regenerating properties. Traditional RA treatments, such as glucocorticoids, NSAIDs, DMARDs, and TNF inhibitors, often have limited efficacy and significant side effects, including myelosuppression, organ damage, and increased cancer risk. MSCs, with their low immunogenicity and ability to home to inflamed tissues, offer a more targeted and effective approach. They can suppress inflammation by modulating immune cells, secreting anti-inflammatory cytokines like TGF-β1, PGE-2, and IL-10, and releasing extracellular vesicles that regulate immune responses. MSCs also promote tissue repair by differentiating into osteoblasts and chondrocytes, aiding in the regeneration of damaged joint tissues. MSCs inhibit pro-inflammatory cytokines such as TNF-α and IL-1β, which are central to RA pathogenesis. They reduce the activity of effector T cells, promote regulatory T cells (Tregs), and inhibit the differentiation of harmful T helper cells (Th17). MSCs also modulate macrophage polarization, shifting them from pro-inflammatory M1 to anti-inflammatory M2 types, which helps reduce joint inflammation. Additionally, MSCs can inhibit B cell proliferation and antibody production, which are key factors in RA progression. The effectiveness of MSCs is enhanced by appropriate inflammatory signals, such as IFN-γ, which improve their immunosuppressive capacity. However, excessive inflammation can impair MSC function, highlighting the need for strategies to optimize the inflammatory microenvironment. MSCs also promote the production of anti-inflammatory cytokines like IL-10 and TGF-β, which help regulate immune responses and reduce joint damage. They can be engineered to express specific molecules, such as CXCR7, to enhance their homing and therapeutic effects. MSCs have been shown to reduce bone erosion and cartilage destruction by inhibiting osteoclast formation and promoting osteoblast differentiation. They also secrete factors that inhibit matrix metalloproteinases (MMPs), which are involved in cartilage and bone degradation. Despite their potential, challenges remain in the clinical application of MSCs for RA, including ensuring their survival and function in the inflammatory joint environment. Strategies such as using hydrogels to deliver MSCs directly to the joint, combining MSCs with antioxidants or other therapeutic agents, and genetic modification to enhance homing and survival are being explored. Overall, MSCs offer a promising approach for RA therapy by combining immunomodulation and tissue regeneration, with ongoing research aimed at improving their efficacy and safety.