Safety and efficacy of autologous, adipose-derived mesenchymal stem cells in patients with rheumatoid arthritis: a phase I/IIa, open-label, non-randomized pilot trial

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 x 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-alpha, 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-alpha, 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.