Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibodies that affect various organ systems. SLE is a chronic autoimmune disease that significantly affects quality of life and has high morbidity and mortality rates.
Current treatment strategies focus on nonspecific anti-inflammatory and immunosuppressive agents to manage immunological disorders, including antimalarial drugs, glucocorticoids, non-corticosteroid immunosuppressants, and targeted therapies. However, current therapeutic strategies, including immunosuppressive and biological agents, have limitations such as low remission rates, significant side effects, and lack of specificity, creating an urgent need for new effective therapies for SLE.
The pathogenesis of SLE involves complex interactions between genetic and environmental factors, leading to immune dysregulation and autoantibody production. The main pathogenic mechanisms include loss of immune tolerance, activation of autoreactive T and B cells, and formation of immune complexes that contribute to tissue damage. Activation of B and T cells triggers the release of autoantibodies such as anti-double-stranded DNA (anti-dsDNA) specific to SLE, particularly lupus nephritis. Excessive use of complement C3 and C4 for the clearance of apoptotic bodies results in decreased levels of C3 and C4 in the blood. In addition, the activation of several pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), further exacerbates the disease.
Mesenchymal stem cell (MSC) therapy has emerged as a promising approach for autoimmune diseases due to its immunomodulatory and anti-inflammatory properties. The secretome derived from umbilical cord MSCs (UCMSC-derived), which consists of bioactive molecules such as cytokines, growth factors, and extracellular vesicles, offers advantages over cell-based therapies, including ease of administration, cost-effectiveness, and lower immunogenicity. The secretome from UCMSC has antiapoptotic, anti-inflammatory, antifibrotic, angiogenic, and tissue regenerative effects, making it a potential treatment for SLE. Preclinical studies have demonstrated the secretome's potential to modulate immune responses and enhance tissue regeneration.
A randomized, double-blind, controlled study was conducted to investigate the efficacy and safety of the secretome from UCMSCs in female patients with SLE who had moderate disease activity. A total of 29 patients were randomly assigned to receive intramuscular injections of 1.5 cc of secretome or placebo (0.9% NaCl) weekly for 6 weeks. Disease activity was assessed using the Mexican systemic lupus erythematosus disease activity index (MEX-SLEDAI) score, complement levels (C3 and C4), proinflammatory cytokine levels interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), as well as anti-dsDNA antibodies, at the start of the study, on day 22, and on day 43.
The results showed a significant decrease in MEX-SLEDAI scores in the secretome group compared to the placebo group (p<0.05). Complement C3 levels increased significantly in the secretome group on day 43, indicating improved immune homeostasis, while C4 levels did not show significant differences between groups. IL-6, TNF-a, and anti-dsDNA levels showed a downward trend in the secretome group, although not statistically significant. No serious side effects were found.
Conclusion:
This study found that the secretome from UCMSC exhibits immunomodulatory and anti-inflammatory effects, thereby reducing disease activity in SLE patients. These findings suggest its potential as a safe and effective adjunctive therapy for SLE, although further studies with larger sample sizes and longer follow-up periods are needed to validate these results.
Image: Illustration
References:
Nurudhin A, Werdiningsih Y, Sunarso I, Marwanta S, Damayani A, Prabowo NA, et al. Umbilical cord mesenchymal stem cell-derived secretome as a potential treatment for systemic lupus erythematosus: A double-blind randomized controlled trial Narra J. 2025; 5(1): e1799.http://doi.org/10.52225/narra.v5i1.1799.
