Human Umbilical Cord Mesenchymal Stem Cell Therapy for Patients with Active Rheumatoid Arthritis: Safety and Efficacy

Abstract

This study was designed to assess the safety and efficacy of human umbilical cord mesenchymal stem cells (UC-MSCs) in the treatment of rheumatoid arthritis (RA). In this ongoing cohort, 172 patients with active RA who had inadequate responses to traditional medication were enrolled. Patients were divided into two groups for different treatment: disease-modifying anti-rheumatic drugs (DMARDs) plus medium without UC-MSCs, or DMARDs plus UC-MSCs group (4×10(7) cells per time) via intravenous injection. Adverse events and the clinical information were recorded. Tests for serological markers to assess safety and disease activity were conducted. Serum levels of inflammatory chemokines/cytokines were measured, and lymphocyte subsets in peripheral blood were analyzed. No serious adverse effects were observed during or after infusion. The serum levels of tumor necrosis factor-alpha and interleukin-6 decreased after the first UC-MSCs treatment (P<0.05). The percentage of CD4(+)CD25(+)Foxp3(+) regulatory T cells of peripheral blood was increased (P<0.05). The treatment induced a significant remission of disease according to the American College of Rheumatology improvement criteria, the 28-joint disease activity score, and the Health Assessment Questionnaire. The therapeutic effects maintained for 3-6 months without continuous administration, correlating with the increased percentage of regulatory T cells of peripheral blood. Repeated infusion after this period can enhance the therapeutic efficacy. In comparison, there were no such benefits observed in control group of DMARDS plus medium without UC-MSCs. Thus, our data indicate that treatment with DMARDs plus UC-MSCs may provide safe, significant, and persistent clinical benefits for patients with active RA.

Overcoming immunoregulatory plasticity of mesenchymal stem cells for accelerated clinical applications

“…In refractory RA patients, MSC therapy induced a short-term reduction in clinical scores, but the clinical improvement was not maintained during the follow-up period; thus, complete remission was not achieved in any patient [35]. In a larger study, MSC therapy provided clinical efficacy in active RA patients for at least 3 months, and additional MSC administrations at 3 months stabilized the disease [36]. Furthermore, in a recent study of MSC therapy in ALS patients, it was demonstrated that immunomodulatory factors secreted by MSCs were predictive of the effectiveness of MSC therapy and could potentially identify the patients responsive to therapy.…”

Umbilical cord-derived mesenchymal stem cells regulate thymic epithelial cell development and function in Foxn1−/− mice

“…In a previous study, we demonstrated that the level of Treg cells increased after UC-MSC treatment in active RA patients. 12 Based on those results, we proposed the novel hypothesis that the efficacy of MSCs in the treatment of autoimmune diseases could be mediated by Treg function in the restoration of the thymic dysfunction in those patients.…”

“…11 Furthermore, umbilical cord derivedMSCs (UC-MSCs) can also increase the percentage of regulatory T cells (Treg cells) in the peripheral blood of treated patients with rheumatoid arthritis. 12 Because Treg cells are primarily generated in the thymus, we hypothesized that the therapeutic efficacy of MSCs could be mediated by regulating thymic function in patients with those diseases. Compared to other sources, UC-MSCs have well-documented self-renewal and multipotent differentiation properties and possess immunoregulatory capacities.…”

Emerging immunotherapies for rheumatoid arthritis

“…One Phase I/ II trial in a cohort of 172 patients with active RA has been completed, showing that treatment with both umbilical cord MSC (UC-MSC) and DMARDs significantly improved the 28-joint DAS for 3-6 mo compared with DMARD treatment alone. 187 These beneficial effects were associated with an increase in peripheral blood Tregs and a decrease in serum TNF and IL-6. It is encouraging that this first MSC trial in RA patients indicates that MSC treatment may provide clinical benefit, but further, larger, (Phase III) trials are required to obtain robust data on their safety and efficacy.…”