Mesenchymal Stem Cell-Based Therapy For Rheumatoid Arthritis – A Review

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation, progressive joint destruction, and immune dysregulation. Although conventional disease-modifying antirheumatic drugs (DMARDs) and biological agents have improved disease management, treatment resistance, adverse effects, and inadequate therapeutic responses remain significant challenges. Mesenchymal stromal cells (MSCs) have emerged as a promising therapeutic approach owing to their immunomodulatory, antiinflammatory, and tissue-regenerative properties. This review discusses the immunopathogenesis of RA, focusing on the roles of B lymphocytes, T lymphocytes, autoantibodies, and pro-inflammatory cytokines in disease progression. It highlights the mechanisms through which MSCs regulate immune responses by promoting regulatory T cells (Tregs), suppressing T-helper 17 (Th17) cell responses, modulating macrophage polarization, and potentially reducing osteoclast-mediated bone destruction. The therapeutic potential of MSCs derived from different tissue sources and the emerging role of MSC-derived extracellular vesicles as cell-free therapeutic alternatives are also examined. Furthermore, current clinical evidence, translational challenges, and future research directions are explored. Preliminary clinical findings suggest potential benefits of MSC-based therapies in patients with refractory RA; however, evidence remains limited by small study populations, heterogeneous cell preparations, and insufficient long-term safety and efficacy data. Standardized manufacturing protocols, reliable potency assays, biomarker-guided patient selection, and well-designed randomized controlled trials are essential to establish their clinical utility. MSC-based therapies represent a promising investigational strategy for RA, but further research is required before their routine clinical application.