The Sufficient Immunoregulatory Effect of Autologous Bone Marrow-Derived Mesenchymal Stem Cell Transplantation on Regulatory T Cells in Patients with Refractory Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is an advanced autoimmune disease described by joint involvement. The special properties of mesenchymal stem cells (MSCs) introduced them as a potential therapeutic candidate for RA. In this study, a single dose of autologous MSCs isolated from bone marrow (autologous BM-MSCs, 1×106 per kg) was injected intravenously into 13 patients suffering from refractory RA who were followed up within 12 months after the intervention to evaluate immunological elements. Our results showed that the gene expression of forkhead box P3 (FOXP3) in peripheral blood mononuclear cells (PBMCs) considerably increased at month 12. We found a substantial increasing trend in the culture supernatant levels of IL-10 and transforming growth factor-beta 1 (TGF-β1) in PBMCs from the beginning of the intervention up to the end. Our data may reflect the sufficient immunoregulatory effect of autologous BM-MSCs on regulatory T cells in patients suffering from refractory RA.

Mesenchymal Stem/Stromal Cells for Rheumatoid Arthritis Treatment: An Update on Clinical Applications

“…A significant decrease in DAS28-ESR, VAS, and ESR up to 12 months was reported [ 43 ]. In contrast to previous clinical trials using MSC-based therapy for RA, no statistically significant differences in serum levels of CRP, anti-CCP, IL-17, and IFN-γ cytokine levels were observed [ 43 , 87 ]. A significant increase in the percentage of regulatory CD4 + T cells one month after MSC infusion was observed.…”

“…A significant increase in the percentage of regulatory CD4 + T cells one month after MSC infusion was observed. The increase of regulatory CD4 + T cells measured by FOXP3 mRNA levels was maintained in parallel to an increase in T-bet and GATA3 transcription factor mRNA levels and IL-10 and TGF-β cytokine levels in the sera 12 months after the MSC infusion [ 87 ]. The authors suggested that the decrease in percentage of regulatory CD4 + T cells in the periphery following MSC infusion suggests that multiple infusions of MSCs or higher dose of MSCs may be required to sustain expansion of in vivo regulatory CD4 + T cells.…”

“…These results were in line with the results found by Wang L et al [ 37 , 42 ] and Yan Y et al (ChiCTR-ONC-16008770) [ 40 ]. They also observed an inverse correlation between the IL-4 cytokine levels in the sera and the DAS28 at 6 months follow-up [ 87 ]. Furthermore, in this clinical trial the authors evaluated for the first time the response of B cells, B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), and their receptors on the surface of B cells, such as B cell activation factor receptor (BR3), transmembrane activator and CAML interactor protein (TACI), and B-cell maturation antigen (BCMA).…”

Multipotent Mesenchymal Stromal Cells in Rheumatoid Arthritis and Systemic Lupus Erythematosus; From a Leading Role in Pathogenesis to Potential Therapeutic Saviors?

“…Twelve-month follow-up showed no adverse effect, a significant decrease in DAS28-ESR, VAS scores and ESR, but no changes in blood inflammatory markers ( 169 ). Systemic injection of autologous BM-MSCs into refractory RA patients with 12 month-follow up demonstrated that the gene expression of forkhead box P3 (FOXP3) in peripheral blood mononuclear cells (PBMCs) was significantly induced ( 170 ). Furthermore, high levels of IL-10 and transforming growth factor-beta 1 (TGF-β1) were noted in the culture supernatant of PBMCs over the time course of treatment ( 170 ).…”

“…Systemic injection of autologous BM-MSCs into refractory RA patients with 12 month-follow up demonstrated that the gene expression of forkhead box P3 (FOXP3) in peripheral blood mononuclear cells (PBMCs) was significantly induced ( 170 ). Furthermore, high levels of IL-10 and transforming growth factor-beta 1 (TGF-β1) were noted in the culture supernatant of PBMCs over the time course of treatment ( 170 ). Autologous BM-MSCs were also used in another study with promising effects, but up to 12 months follow up ( 171 ).…”