Umbilical Cord Mesenchymal Stromal Cell Secretome for Moderate Rheumatoid Arthritis (SECRETOME-RA)

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by persistent synovial inflammation, progressive cartilage destruction, bone erosion, and functional disability. Although conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) remain the standard treatment, a substantial proportion of patients continue to experience active disease, highlighting the need for adjunctive therapeutic strategies.

Umbilical cord-derived mesenchymal stromal cell (UC-MSC) secretome is a cell-free biological product containing cytokines, growth factors, extracellular vesicles, and other bioactive molecules with immunomodulatory, anti-inflammatory, and regenerative properties. Compared with live-cell therapy, secretome-based treatment may offer advantages including lower immunogenicity, easier storage and transportation, and standardized manufacturing.

This prospective, randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the efficacy and safety of intramuscular UC-MSC secretome administered in combination with stable csDMARD therapy in patients with moderate rheumatoid arthritis. Participants were randomly assigned to receive either UC-MSC secretome or placebo in addition to standard treatment. The intervention consisted of six weekly intramuscular injections, followed by protocol-defined clinical and safety follow-up.

The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology 20% improvement response (ACR20). Key secondary endpoints included ACR50 and ACR70 response rates, changes in inflammatory biomarkers (including TNF-α, IL-6, and TGF-β), disease activity, patient-reported outcomes, and treatment safety.