Abstract
OBJECTIVE: The present study is a phase I/IIa non-randomized, open-label study to evaluate safety and efficacy of a single, intravenous infusion of autologous, adipose-derived mesenchymal stem cells (adMSCs) over a period of 52 weeks, in patients with active rheumatoid arthritis (RA). METHODS: 15 eligible RA patients aged 18-65 years were enrolled and followed up at weeks 4, 12, 26 and 52 after receiving a single intravenous dose of 2 × 10(8) adMSCs. Efficacy was examined using American College of Rheumatology (ACR66/68 score) criteria for swollen and tender joint counts (S/TJC), and serum TNF-α, IL-6, CRP, and ESR levels. Safety endpoints included measures of hematologic, hepatic, and renal function. RESULTS: ACR66/68 scores for both S/TJC showed significant improvements with large effect sizes (ES) at week 52 vs baseline (p < 0.01, ES = 0.83 and p < 0.001, ES = 0.93 respectively). Medium to large ES were also obvious for ACR66/68 scores measured at other timepoints. Levels of inflammatory markers, TNF-α, IL-6 and ESR remained unchanged compared to baseline. However, a difference in CRP levels with a small effect size was observed at week 4 (p = 0.229, ES = 0.33) with further improvement at week 52 (p = 0.183, ES = 0.37). Post-intervention, levels of hematologic, hepatic, and renal function remained largely unchanged (p > 0.05). No acute or long-term serious adverse events (AEs) occurred. CONCLUSIONS: The results indicated that a single, intravenous administration of autologous adMSCs is safe and efficacious for improvement in joint function in patients with active RA. Data from the current study supports the exploration of ad-MSCs as a therapeutic intervention for RA. Trial Registration Clinical trial registration number: NCT03691909. Registered September 27, 2018- Retrospectively registered ( https://clinicaltrials.gov/show/NCT03691909 ).