Abstract
The immunosuppressive and anti-inflammatory properties of mesenchymal stem/stromal cells (MSCs) have prompted their therapeutic application in several autoimmune diseases, including rheumatoid arthritis (RA). MSCs derived from bone marrow and adipose tissue has earlier been tried with limited success. However, Wharton's jelly present in human umbilical cord is discarded after delivery which makes a rich source of MSCs with least ethical issues. The immunomodulatory properties of human umbilical cord-derived MSCs (UC-MSCs) were evaluated in-vitro on the mononuclear cells from synovial fluid (SF) and peripheral blood of RA patients. The therapeutic potential of UC-MSCs was checked by transplanting the cells in rats with collagen-induced arthritis (CIA). MSCs isolated from Wharton's Jelly significantly suppressed the proliferation and activation of lymphocytes from both peripheral blood as well as SF of RA patients, down-modulated the functions of activated CD4+, CD8+ T-cells, suppressed the secretion of pro-inflammatory cytokines, and induced the expansion of T-regulatory cells. Xenotransplantation of UC-MSCs in CIA rats clearly indicated a sustained impact in terms of slowing down the progression of disease activity and reversal of arthritic processes along with triggering of joint tissue repair mechanisms, which could be observed till 6 weeks post-transplantation. The results from the current study suggest that human umbilical cord is a rich source of MSCs for allotransplantation. The UC-MSCs may be used successfully as a cell-based therapeutic option either in isolation or in conjunction with existing therapeutic drugs not only to relieve the joint inflammation but also regenerate the damaged bone and cartilage tissues in arthritis. Relevance to patients: The current study highlights the potential use of MSCs as a cell-based therapeutic option for the treatment of inflammatory RA.