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

• Published in: Stem cells translational medicine Vol. 7; no. 9; pp. 636 - 642
• Main Authors: Park, Eun Hye, Lim, Hee‐suk, Lee, Seunghee, Roh, Kyounghwan, Seo, Kwang‐Won, Kang, Kyung‐Sun, Shin, Kichul
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-09-2018; Oxford University Press
• Subjects: Aged; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - pathology; Arthritis, Rheumatoid - therapy; Blood Sedimentation; Bone marrow; C-Reactive Protein - analysis; Clinical trial; Clinical trials; Cord blood; Cytokines; Cytokines - blood; Disease; Erythrocyte sedimentation rate; Female; Fetal Blood - cytology; Health Status; Human Clinical; Humans; Immunomodulation; Infusions, Intravenous; Intravenous administration; Joint diseases; Male; Mesenchymal stem cell; Mesenchymal Stem Cell Transplantation; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mesenchyme; Methotrexate; Methotrexate - therapeutic use; Middle Aged; Patients; Questionnaires; Rheumatoid arthritis; Safety; Severity of Illness Index; Stem cells; Studies; Toxicity; Treatment Outcome; Tumor necrosis factor; Umbilical cord; Umbilical cord blood; Mesenchymal stem cell; Clinical trial; Safety; Umbilical cord blood; Rheumatoid arthritis
• ISSN: 2157-6564; 2157-6580
• DOI: 10.1002/sctm.18-0031

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
This is a phase Ia clinical trial to asses the safety of human umbilical cord blood‐derived mesenchyaml stem cells (hUCB‐MSCs) infusions in patients with rheumatoid arthritis (RA). Nine patients with RA were given a single infusion of hUCB‐MSCs, cell numbers up to 1 × 108, and no ominous short‐term safety signal was observed.