Umbilical Cord Mesenchymal Stromal Cell Secretome for Moderate Rheumatoid Arthritis: A Randomized Double-Blind Placebo-Controlled Trial

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.

Inclusion criteria

• -Adults aged 18 to 60 years.
• Diagnosis of rheumatoid arthritis according to the 2010 ACR/EULAR Classification Criteria.
• Moderate disease activity (DAS28-CRP >3.2 and ≤5.1).
• Receiving stable conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy for at least 3 months before enrollment.
• Stable dose of corticosteroids and/or NSAIDs for at least 4 weeks before enrollment, if applicable.
• Willing and able to provide written informed consent.

Exclusion criteria

• Other autoimmune rheumatic diseases or overlap syndromes.
• Active tuberculosis or other severe active infections.
• Active hepatitis B, hepatitis C, or HIV infection.
• History of malignancy.
• Severe renal impairment or severe hepatic dysfunction.
• Uncontrolled diabetes mellitus or uncontrolled cardiovascular disease.
• Pregnancy or breastfeeding.
• Known hypersensitivity to the study intervention or its components.
• Participation in another interventional clinical trial within the previous 3 months.