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

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 × 108 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).

Comprehensive Analysis of Novel Genes and Pathways Associated with Osteogenic Differentiation of Adipose Stem Cells

“…The ability to self-renew, the proliferation potential, and the multipotency of ADSCs make them attractive for regenerative medicine applications [ 23 , 24 ]. Since ADSCs are readily available and easy to obtain in large quantities, they have become promising seed cells for bone tissue engineering [ 25 ]. In order for ADSC-based therapies to be successful in vivo, they must be paired with a substance that facilitates their osteogenic differentiation in vivo [ 26 ].…”

Mesenchymal Stromal Cells: New Generation Treatment of Inflammatory Bowel Disease

“…156 Similarly, it has also been extensively studied in refractory systemic lupus erythematosus, 157 graft-versus-host disease 158 and rheumatoid arthritis. 159 MSCs show a dual role in immunoregulation. MSCs recognize different danger signals through TLRs.…”

Mesenchymal Stem/Stromal Cells for Treatment of Rheumatoid Arthritis

“…This study also lays the foundation for prospective studies to further explore the use of ADSCs as a therapeutic modality for patients suffering with active RA. 11 3. Allogenic MSCs and RA…”

“…T cells, dendritic cell maturation and NK cell activity; and promote regeneration contribute to the beneficial effects noted in several preclinical inflammatory studies. 10,11 Specifically, MSCs have been highlighted as a promising alternative for treatment of several immune-related diseases, such as graft-vs-host disease (GVD), multiple sclerosis, inflammatory bowel disease, atopic dermatitis, etc. 10 In addition, they have been associated to have therapeutic potential in preclinical models of RA.…”

“…10 In addition, they have been associated to have therapeutic potential in preclinical models of RA. 11 The goal of this review is to highlight the safety and efficacy of both autologous as well as allogenic MSCs to treat RA based on recently published clinical studies.…”