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Stem Cells Transl Med. 2018 Sep;7(9):636-642. doi: 10.1002/sctm.18-0031. Epub 2018 Aug 15.

Intravenous Infusion of Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Rheumatoid Arthritis: A Phase Ia Clinical Trial.

Author information

1
Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
2
Division of Rheumatology, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, South Korea.
3
Institute for Stem cell Regenerative Medicine, Kangstem Biotech, Seoul, South Korea.
4
Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.

Abstract

Based on immunomodulatory actions of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs), in vitro or preclinical studies of hUCB-MSCs have been conducted extensively in rheumatoid arthritis (RA). However, few human trials have investigated the outcomes of hUCB-MSC infusions. The CURE-iv trial was a phase I, uncontrolled, open label trial for RA patients with moderate disease activity despite treatment with methotrexate. The patients received a single intravenous infusion of 2.5 × 107 , 5 × 107 , or 1 × 108 cells of hUCB-MSCs for 30 minutes, three patients in each cluster, with an increment of cell numbers when there was no dose-limited adverse event. Clinical and safety assessments were performed during the study period, and serum cytokines were measured at baseline and 24 hours after the infusion. Out of 11 screened RA patients, 9 were enrolled. The participants were predominantly female (78%) and the mean age was 57.4 years. The mean disease duration was 9.5 years, and baseline 28-joint disease activity score (DAS28; using erythrocyte sedimentation rate) was 4.53. There was no major toxicity in all clusters up to 4 weeks after the infusion. Serum erythrocyte sedimentation rate changes at 4 weeks (n = 9) were -7.9 ± 10.4 (p = .0517) and DAS28 changes were -1.60 ± 1.57 (p = .0159). Reduced levels of IL-1β, IL-6, IL-8, and TNF-α at 24 hours were observed in the cluster infused with 1 × 108 MSCs. This phase Ia hUCB-MSC infusion trial for established RA patients revealed no short-term safety concerns. Stem Cells Translational Medicine 2018.

KEYWORDS:

Clinical trial; Mesenchymal stem cell; Rheumatoid arthritis; Safety; Umbilical cord blood

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