Background/Purpose: The immunomodulatory actions of human umbilical cord blood (hUCB)-derived mesenchymal stem cells (MSCs) in rheumatoid arthritis (RA) have been studied extensively via in vitro or pre-clinical studies, yet few human trials have been conducted investigating the outcome of hUCB-derived MSC infusion.

Methods: The CURE-iv (Clinical and safety assessment of human Umbilical cord blood-derived mesenchymal stem cell therapy for RhEumatoid arthritis patients administered intravenously) trial was a phase 1, proof-of-concept clinical trial for RA patient with moderate disease activity despite treatment with methotrexate. Patients meeting the 2010 ACR/EULAR classification criteria and with a DAS28-ESR >3.2 were eligible for the trial. Subjects were each given a single intravenous infusion of 2.5 x 10⁷, or 5 x 10⁷, or 1 x 10⁸ cells of hUCB-derived MSCs for 30 minutes; 3 patients in each cluster, with increment of cell numbers when there was no dose-limited adverse events. Clinical and safety parameters were monitored and followed after the infusion period (first 24 hours, 72 hours, 1 week, and 4 weeks). Serum cytokines at baseline and 24 hours after the infusion were analyzed.

Results: Eleven RA patients were screened, 9 of which were enrolled from a single center. The mean age was 57.4 years, 78 % being female, with a disease duration of 9.5 ± 8.7 years, and DAS28-ESR 4.53 ± 1.35. There was no ominous safety signal in all clusters up to 4 weeks after the infusion. One patient stated joint pain 60 min after the infusion (5 x 10⁷ group), but it was thought to be unrelated to the investigational product. ESR and CRP changes at 4 weeks (n=9) were -7.89 ± 10.36 (p= 0.0517), and -0.37 ± 1.09 (p=0.3362). DAS28 and HAQ changes at 4 weeks were -1.60 ± 1.57 (p= 0.0159), and -0.15 ± 0.48 (p= 0.3706), respectively. One patient in the 1 x 10⁸ group showed substantial decrease in all serum levels of IL-1b, IL-6, IL-8, and TNF-a.

Conclusion: This phase 1 clinical trial – a single dose intravenous infusion of hUCB-derived MSCs – for established RA patients was completed without any short-term safety concerns (NCT02221258).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/intravenous-infusion-of-umbilical-cord-blood-derived-mesenchymal-stem-cells-in-rheumatoid-arthritis-a-phase-1-proof-of-concept-clinical-trial/