Application of cell therapy in rheumatoid Arthritis: Focusing on the immunomodulatory strategies of Mesenchymal stem cells

Rheumatoid arthritis (RA) is a common chronic autoimmune disease that primarily affects the joints, leading to synovial inflammation and hyperplasia, which subsequently causes joint pain, swelling, and damage. The microenvironment of RA is characterized by hypoxia, high reactive oxygen species (ROS), low pH, and levels of high inflammatory factors. Traditional treatments only partially alleviate symptoms and often cause various adverse reactions with long-term use. Therefore, there is an urgent need for safer and more effective treatments. In recent years, mesenchymal stem cells (MSCs) have shown significant potential in treating RA due to their diverse immunomodulatory mechanisms. MSCs paracrine a variety of soluble factors to improve the inflammatory microenvironment in RA patients by inhibiting T cell proliferation or inducing T cell differentiation to regulatory T cells (Tregs), inhibiting B cell proliferation and differentiation and immunoglobulin production, prompting macrophage polarization toward an anti-inflammatory phenotype, and inhibiting neutrophil recruitment and preventing the maturation of dendritic cells (DCs). This review summarizes the immunomodulatory effects of MSCs in RA and their application in animal models and clinical trials. Although the immunomodulatory mechanisms of MSCs are not yet fully elucidated, their significant potential in RA treatment has been widely recognized. Future research should further explore the immunomodulatory mechanisms of MSCs and optimize their functions in different pathological microenvironments to develop more effective and safer therapeutic strategies.