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

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

Relationship between dietary magnesium intake and rheumatoid arthritis in US women: a cross-sectional study

“…Nine 2-year-cycle data from the continuous NHANES (1999-2016) were combined for analysis with greater statistical reliability (n=92 062). We excluded men (n=45 336), participants younger than 18 years (n=19 087) or older than 80 years of age (n=919), [22][23][24][25] participants who had been diagnosed with other forms of arthritis, participants with missing RA data (n=3438) or dietary magnesium information (n=9958), and 13 324 participants were eventually included in the analysis (figure 1).…”

Mesenchymal stem cells: amazing remedies for bone and cartilage defects

“…Evaluation of BM-MSC therapy on the healing of joints in animals with induced RA demonstrated that inflammation, joint swelling, and destruction of cartilage reduced significantly compared with an arthritic non-treated group [ 223 ]. Park and coworkers in the first human trial of hUCB-MSCs in patients with RA observed no major toxicity, serious adverse event, or major abnormalities in serum chemicals or hematologic profiles, both during and after the treatment [ 224 ]. Allogenic UC-MSCs transplantation in mice model of RA prevented arthritis progression by suppressing T follicular helper (Tfh) cells proliferation [ 220 ].…”

Immunomodulatory effect of human bone marrow‐derived mesenchymal stromal/stem cells on peripheral blood T cells from rheumatoid arthritis patients

“…Thus, a possible therapeutic approach that is beginning to be explored is the use of mesenchymal stromal/stem cells (MSCs), which have already shown evidences of clinical improvements in other autoimmune diseases, namely, systemic lupus erythematosus (X. Li, Wang, Liang, Zhang, & Sun, ; Liang et al, ; Wang et al, ) and multiple sclerosis (Connick et al, ; Karussis et al, ). Recently, clinical trials, using umbilical cord blood (UCB)‐derived (Park et al, ) and bone marrow (BM)‐derived MSC (Ghoryani et al, ) for the treatment of RA patients, demonstrated that MSC‐based therapy reduced DAS28 score, decreased the percentage of peripheral blood (PB) Th17 cells and serum levels of IL‐1β, IL‐6, IL‐8, and TNFα, while increasing PB regulatory T (Treg) cells percentage and IL‐10 in serum. These clinical trials showed evident clinical benefits for the RA patients under MSCs treatment (Ghoryani et al, ; Park et al, ).…”

“…Recently, clinical trials, using umbilical cord blood (UCB)‐derived (Park et al, ) and bone marrow (BM)‐derived MSC (Ghoryani et al, ) for the treatment of RA patients, demonstrated that MSC‐based therapy reduced DAS28 score, decreased the percentage of peripheral blood (PB) Th17 cells and serum levels of IL‐1β, IL‐6, IL‐8, and TNFα, while increasing PB regulatory T (Treg) cells percentage and IL‐10 in serum. These clinical trials showed evident clinical benefits for the RA patients under MSCs treatment (Ghoryani et al, ; Park et al, ). MSCs have also provided promising results in collagen‐induced arthritis in mice, wherein MSC treatment delayed the disease onset, reduced the paw swelling and the infiltration of immune cells into the joints, and abolished the arthritis progression.…”