Transplantation of CTLA4Ig gene‐transduced adipose tissue‐derived mesenchymal stem cells reduces inflammatory immune response and improves Th1/Th2 balance in experimental autoimmune thyroiditis

Abstract

Although CTLA4Ig-MSC transplantation had better result in reduction of serum TgAA, both of ATMSC and CTLA4Ig-MSC transplantations are promising treatments for autoimmune thyroiditis judging from the results of histopathology and cytokine analysis. They may be attractive candidates for treating organ-specific autoimmune disease.

Allogeneic Murine Mesenchymal Stem Cells: Migration to Inflamed Joints In Vivo and Amelioration of Collagen Induced Arthritis When Transduced to Express CTLA4Ig

“…In this study, we see significant suppression of IFNg when MSCs expressing CTLA4Ig are cultured with T cells at both 24 and 72 h. This reflects the known effects of MSCs on suppressing IFNg production and the reported reduction in systemic IFNg post-CTLA4Ig therapy in RA patients [52]. It is also known that MSCs expressing CTLA4Ig may be used to alter the Th1:Th2 cytokine profile to favour Th2 cytokine production and ameliorate experimental autoimmune thyroiditis [34]. It is likely that MSCs and CTLA4Ig act syngertistically to alter suppress T cell activation, reduce production of IFNg and cause a shift towards a Th2 cytokine response in inflammatory arthritis.…”

“…The use of allogeneic cells would increase the potential use of this therapy and therefore, the use of MHC mismatched MSCs [18] was used to determine migration to the joint in vivo and the impact of allogeneic MSCs secreting CTLA4Ig on disease progression in CIA in DBA/1 mice. CTLA4Ig is currently licensed for clinical use in RA and MSCs expressing CTLA4Ig have been shown to be of therapeutic benefit in animal models of graft versus host disease [33] and autoimmune thyroiditis [34]. The cotransfection of MSCs may also be used to facilitate other gene therapy strategies.…”

Adult stem cells: Simply a tool for regenerative medicine or an additional piece in the puzzle of human aging?

“…the ability of haDSCs to downregulate th1 cytokines has been recently demonstrated in experimental autoimmune thyroiditis. 5 Systemic infusion of haDSCs prevents lymphocyte infiltration to thyroid glands, decreases the production of pro-inflammatory cytokines and improves the th1/th2 balance. Similar to MSCs, haDSCs can suppress t-cell proliferation and cytokine production in response to alloantigens and non-specific antigens and can inhibit the function of B-, natural killer-and dendritic cells.…”

Transplantation of Adipose Tissue-Derived Mesenchymal Stem Cells Prevents the Development of Lupus Dermatitis

“…Recent studies on successful MSC treatment in autoimmune diseases have been reported. Further, in our previous studies on autoimmune thyroiditis and rheumatoid arthritis, CTLA4Ig-ASCs showed stronger suppression in the T cell proliferation against autoantigens and were more effective in reducing serum levels of autoantibodies than non-transduced ASCs were [17][18][19].…”