Mesenchymal Stem Cell-Conditioned Medium Reduces Disease Severity and Immune Responses in Inflammatory Arthritis

Abstract

We evaluated the therapeutic potential of mesenchymal stem cell-conditioned medium (CM-MSC) as an alternative to cell therapy in an antigen-induced model of arthritis (AIA). Disease severity and cartilage loss were evaluated by histopathological analysis of arthritic knee joints and immunostaining of aggrecan neoepitopes. Cell proliferation was assessed for activated and naïve CD4+ T cells from healthy mice following culture with CM-MSC or co-culture with MSCs. T cell polarization was analysed in CD4+ T cells isolated from spleens and lymph nodes of arthritic mice treated with CM-MSC or MSCs. CM-MSC treatment significantly reduced knee-joint swelling, histopathological signs of AIA, cartilage loss and suppressed TNFα induction. Proliferation of CD4+ cells from spleens of healthy mice was not affected by CM-MSC but reduced when cells were co-cultured with MSCs. In the presence of CM-MSC or MSCs, increases in IL-10 concentration were observed in culture medium. Finally, CD4+ T cells from arthritic mice treated with CM-MSC showed increases in FOXP3 and IL-4 expression and positively affected the Treg:Th17 balance in the tissue. CM-MSC treatment reduces cartilage damage and suppresses immune responses by reducing aggrecan cleavage, enhancing Treg function and adjusting the Treg:Th17 ratio. CM-MSC may provide an effective cell-free therapy for inflammatory arthritis.

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

“…The ability of MSCs to favor CD4 + CD25 + FoxP3 + Treg cells' differentiation and/or enhance their activity is broadly described in the literature, and some of the mechanistic basis of these processes are also well elucidated (Duffy, Ritter, Ceredig, & Griffin, ; Griffin, Ritter, & Mahon, ). Recent studies give further evidences that human MSCs support the induction of Treg polarization either in PBMCs from RA patients in vitro (Ma et al, ), as well as in collagen‐induced arthritis mice model, both in vitro and in vivo (Kay et al, ; Ma et al, ; Nam et al, ; Yu et al, ). Nevertheless, MSCs are also known to be highly sensitive to the surrounding microenvironment; accordingly, different conditions in the experimental protocols of in vitro or in vivo assays are likely to affect MSCs immunomodulatory behavior.…”

Conditioned medium of mesenchymal stem cells delays osteoarthritis progression in a rat model by protecting subchondral bone, maintaining matrix homeostasis, and enhancing autophagy

“…Considering all these secretions are contained in MSCs' culture medium, also known as conditioned medium (CM; Soleimanifar et al, 2018), it is a safer choice to use cell-free CM as a substitute for MSCT. Increasing publications have demonstrated the effectiveness of cell-free CM in ameliorating high glucose-induced degradation of ECM (Qi et al, 2018), inflammatory arthritis (Kay et al, 2017), wound healing (Amini et al, 2018), and spinal cord injury (Kanekiyo et al, 2018). Considering the regenerative property of CM, we therefore measured the potential of CM against OA in a rat model.…”

Manipulated Mesenchymal Stem Cells Applications in Neurodegenerative Diseases

“…The use of conditioned medium in antigen-induced arthritis (AIA) significantly lessened knee swelling, cartilage loss, and some other pathological signs of AIA. It also inhibited TNF-α production and increased IL-10 production through enhancing Treg cell functions (94).…”