Amelioration of clinical symptoms of patients with refractory rheumatoid arthritis following treatment with autologous bone marrow-derived mesenchymal stem cells: A successful clinical trial in Iran

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

“…Rheumatoid arthritis (RA) is an inflammatory, chronic, systemic, and autoimmune disease, characterized by a persistent symmetric polyarthritis (synovitis) that affects mainly the hands and feet, though any joint coated with a synovial membrane can be affected (Chen et al, ; Franceschetti & De Bari, ). RA has an incidence of around 0.5–1.0% in the adult world population, affecting especially women (Firestein, ; Ghoryani et al, ; Kourilovitch, Galarza‐Maldonado, & Ortiz‐Prado, ; Smolen, Aletaha, & McInnes, ), and though its etiology is still unknown, it recognizes the important role played by genetic factors, hormones, infections, gut microbiome, and environmental factors (e.g., smoking and exposure to silica dust; Boissier, Semerano, Challal, Saidenberg‐Kermanac'h, & Falgarone, ; Klareskog, Catrina, & Paget, ; Smolen et al, ).…”

“…The inflammatory cells infiltrating the joints comprise Th1 and Th17 cells; B cells, plasmablasts, and plasma cells; innate lymphoid cells, dendritic cells (DCs), monocytes/macrophages, mast cells, and neutrophils. These immune cells play a critical role in joint damage by producing proinflammatory cytokines—interferon (IFN)γ, interleukin (IL)‐2, IL‐17, tumor necrosis factor (TNF)‐α, granulocyte macrophage colony‐stimulating factor, IL‐1, IL‐6, IL‐15, and IL‐18—free radicals, and extracellular matrix‐degrading enzymes, leading to the chronic inflammation of the joints, subsequent cartilage destruction, and bone erosion (Davignon et al, ; Firestein, ; Ghoryani et al, ; Gonzalez, Gonzalez‐Rey, Rico, Buscher, & Delgado, ; Leyendecker, Pinheiro, Amano, & Bueno, ; Noack & Miossec, ; Smolen et al, ).…”

“…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.…”

Oral Mesenchymal Stem/Progenitor Cells: The Immunomodulatory Masters

“…Due to the immunomodulatory function and low immunogenicity of MSCs, autologous/allogenic MSCs obtain good results in the treatment of human autoimmune and inflammatory diseases. Clinical efficacy and safety have been demonstrated for MSCs applied in patients with systematic lupus erythematosus [143][144][145], rheumatic arthritis [146], GVHD [147], and osteoarthritis, [148] via intravenous or local injection, with the results of a decrease in the disease activity score, rebuilding of T cell imbalance, and functional improvement. Nevertheless, despite the inspiring outcomes in clinical trials, it was proposed that MSC transplantation might not be effective in refractory patients in a long-term perspective [149,150].…”