Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis

Abstract

IntroductionRheumatoid arthritis (RA) is a T-cell-mediated systemic autoimmune disease, characterized by synovium inflammation and articular destruction. Bone marrow mesenchymal stem cells (MSCs) could be effective in the treatment of several autoimmune diseases. However, there has been thus far no report on umbilical cord (UC)-MSCs in the treatment of RA. Here, potential immunosuppressive effects of human UC-MSCs in RA were evaluated.MethodsThe effects of UC-MSCs on the responses of fibroblast-like synoviocytes (FLSs) and T cells in RA patients were explored. The possible molecular mechanism mediating this immunosuppressive effect of UC-MSCs was explored by addition of inhibitors to indoleamine 2,3-dioxygenase (IDO), Nitric oxide (NO), prostaglandin E2 (PGE2), transforming growth factor β1 (TGF-β1) and interleukin 10 (IL-10). The therapeutic effects of systemic infusion of human UC-MSCs on collagen-induced arthritis (CIA) in a mouse model were explored.ResultsIn vitro, UC-MSCs were capable of inhibiting proliferation of FLSs from RA patients, via IL-10, IDO and TGF-β1. Furthermore, the invasive behavior and IL-6 secretion of FLSs were also significantly suppressed. On the other hand, UC-MSCs induced hyporesponsiveness of T cells mediated by PGE2, TGF-β1 and NO and UC-MSCs could promote the expansion of CD4+ Foxp3+ regulatory T cells from RA patients. More importantly, systemic infusion of human UC-MSCs reduced the severity of CIA in a mouse model. Consistently, there were reduced levels of proinflammatory cytokines and chemokines (TNF-α, IL-6 and monocyte chemoattractant protein-1) and increased levels of the anti-inflammatory/regulatory cytokine (IL-10) in sera of UC-MSCs treated mice. Moreover, such treatment shifted Th1/Th2 type responses and induced Tregs in CIA.ConclusionsIn conclusion, human UC-MSCs suppressed the various inflammatory effects of FLSs and T cells of RA in vitro, and attenuated the development of CIA in vivo, strongly suggesting that UC-MSCs might be a therapeutic strategy in RA. In addition, the immunosuppressive activitiy of UC-MSCs could be prolonged by the participation of Tregs.

Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow-Derived Mesenchymal Stem Cells

“…For example, MSC derived from adipose tissues or bone marrow have been used to treat experimental allergic encephalitis, inflammatory bowel disease, immune-mediated arthritis, airway inflammation, and graft-versus-host disease in rodent models [1,[9][10][11][12]. In addition, human MSC have been administered to rodent models of inflammatory diseases [13][14][15][16][17]. Thus, it is apparent that the immune modulatory properties of MSC can be utilized therapeutically in a number of different diseases settings.…”

“…Numerous studies have investigated the underlying mechanisms that drive the immune modulatory properties of both human and mouse MSC [16,[18][19][20]. In human MSC, the reported pathways of immune suppression by MSC include the indoleamine 2,3-deoxygenase (IDO) [21,22], cyclooxygenase [23][24][25], TGF-b [26], soluble IL-1Ra [27,28], soluble MHC [29,30], and the PD-L1 pathways [31,32].…”

The effect of mesenchymal stem cells on dynamic changes of T cell subsets in experimental autoimmune uveoretinitis

“…The mechanisms underlying these effects are largely unknown, but are likely to be mediated by soluble factors [4,5]. These immunosuppressive properties have been exploited extensively in a number of experimental autoimmune diseases and translated recently to the clinical setting in several diseases, such as systemic lupus erythematosus (SLE) [6], Crohn's disease [7], multiple sclerosis (MS) [8], rheumatoid arthritis [9] and Sjögren's syndrome [10]. In autoimmune diseases, MSCs can inhibit both T helper type 1 (Th1) and Th17 responses and modulate the Th17/Treg balance [11,12].…”

Adipose Tissue-Derived Mesenchymal Stem Cells: A Novel Therapy in Orthopedics

“…When compared to enzymatically derived MSCs, mechanically derived MSCs have superior differentiation potential with larger secretome content and more diverse exosome content without disruption of vascular stroma [66,67]. This method is purely mechanical with no chemical additives used; thus, showing promising results that power the method of nonenzymatic harvesting of stem cells derived adipose tissue [19,[68][69][70][71][72].…”