Mesenchymal stem cells, autoimmunity and rheumatoid arthritis

Abstract

The vast majority of literature pertaining to mesenchymal stem cells (MSC) immunomodulation has focussed on bone marrow-derived MSC that are systemically infused to alleviate inflammatory conditions. Rheumatoid arthritis (RA) is the commonest autoimmune joint disease that has witnessed significant therapeutic advances in the past decade, but remains stubbornly difficult to treat in a subset of cases. Pre-clinical research has demonstrated that bone marrow, adipose, synovial and umbilical cord-derived MSC all suppress the functions of different immune cells thus raising the possibility of new therapies for autoimmune diseases including RA. Indeed, preliminary evidence for MSC efficacy has been reported in some cases of RA and systemic lupus erythromatosis. The potential use of bone marrow-MSC (BM-MSC) for RA therapy is emerging but the use of synovial MSC (S-MSC) to suppress the exaggerated immune response within the inflamed joints remains rudimentary. Synovial fibroblasts that are likely derived from S-MSCs, also give rise to a cell-cultured progeny termed fibroblast-like synoviocytes (FLS), which are key players in the perpetuation of joint inflammation and destruction. A better understanding of the link between these cells and their biology could be a key to developing novel MSC-based strategies for therapy. The review briefly focuses on BM-MSC and gives particular attention to joint niche synovial MSC and FLS with respect to immunoregulatory potential therapy roles.

Olfactory ecto-mesenchymal stem cells possess immunoregulatory function and suppress autoimmune arthritis

“…[5][6][7] To date, bone marrow-derived MSCs (BM-MSCs) are among the most commonly used MSCs in pre-clinical research for the treatment of rheumatoid arthritis (RA) and other autoimmune diseases. [8][9][10] However, there are some limitations associated with BM-MSCs in clinical applications, including the technical difficulty in acquiring sufficient numbers of cells for therapy. 11 Recently, olfactory ecto-mesenchymal stem cells (OE-MSCs), a new type of resident stem cell in the olfactory lamina propria, have been characterized.…”

Overexpression of soluble RAGE in mesenchymal stem cells enhances their immunoregulatory potential for cellular therapy in autoimmune arthritis

“…Although autophagy induction in MSCs can optimize their clinical application by inhibiting the prevention of apoptosis282930 and MSC treatment has potential therapeutic activity in RA31, MSCs fail to inhibit the immune modulation involved in the inflammatory condition of autoimmune arthritis21. MSCs in proinflammatory niches have immunoregulatory properties that can be induced by inflammatory cytokines such as tumor necrosis factor-α and establish an immunosuppressive microenvironment32.…”

Efficacy of SSEA-3 Positive Cells Derived from Synovial Tissue in Rheumatoid Arthritis

“…Especially, SFMSCs extracted from healthy subjects are able to inhibit T-cell proliferation [25]. However, immunomodulatory function of SFMSCs and SSEA-3 positive cells may be disturbed and cause an inefficacy of SFMSCs and SSEA-3 positive cells in inflammatory environment like uncontrolled RA [41]. In RA synovial tissue, fibroblast-like synoviocytes (FLS) are key players in the perpetuation of joint inflammation and destruction.…”