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

Ridhima Vij, Kevin A Stebbings, Hosu Kim, Hyeonggeun Park, Donna Chang, Ridhima Vij, Kevin A Stebbings, Hosu Kim, Hyeonggeun Park, Donna Chang

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://ichgcp.net/clinical-trials-registry/NCT03691909 ).

Keywords: Adipose-derived mesenchymal stem cell; Autologous; Clinical trial; Efficacy; Intravenous; Rheumatoid arthritis.

Conflict of interest statement

Ridhima Vij and Kevin Stebbings were the employees of Hope Biosciences Stem Cell Research Foundation, and declare that they have no competing interests that could have appeared to influence the work reported in this paper. Hosu Kim, Hyeonggeun Park and Donna Chang declare the following financial interests which may be considered as potential competing interests. The above listed authors are employees of Hope Biosciences LLC.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study flow diagram
Fig. 2
Fig. 2
Joint Counts. Swollen joint count showed a significant decrease at each of the follow-up visits compared to baseline. Tender joint scores showed highly significant decline at all follow-up weeks, compared to baseline. Significance defined at p value ≤ 0.01 (Holm–Šídák correction for multiple comparisons), *p value < 0.01; **p value < 0.001; Wilcoxon-signed rank test
Fig. 3
Fig. 3
Inflammatory parameters. Levels of inflammatory cytokines, TNF-α or IL-6 did not show any significant changes at the follow up visits compared to baseline (a, b). No significant changes were seen in either ESR or CRP levels (c, d). Significance defined at p value ≤ 0.01 (Holm–Šídák correction for multiple comparisons); Wilcoxon-signed rank test

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