Adipose‐Derived Mesenchymal Stem Cells Exert Antiinflammatory Effects on Chondrocytes and Synoviocytes From Osteoarthritis Patients Through Prostaglandin E₂

Abstract

Results. All the inflammatory factors analyzed were down-modulated at the messenger RNA or protein level independently by all 3 AD-MSC sources or by allogeneic AD-MSCs used in coculture with chondrocytes or synoviocytes. Inflammatory factor downmodulation was observed only when AD-MSCs were cocultured with chondrocytes or synoviocytes that produced high levels of inflammatory factors, but no effect was observed in cells that produced low levels of those factors, thus highlighting a dependence of the AD-MSC effect on existing inflammation. The immunomodulators IL-10, IL-1 receptor antagonist, fibroblast growth factor 2, indoleamine 2,3-dioxygenase 1, and galectin 1 were not involved in AD-MSC effects, whereas the cyclooxygenase 2 (COX-2)/prostaglandin E 2 (PGE 2 ) pathway exerted a role in the mechanism of antiinflammatory AD-MSC action.Conclusion. The antiinflammatory effects of ADMSCs are probably not dependent on AD-MSC adipose tissue sources and donors but rather on the inflammatory status of OA chondrocytes and synoviocytes. AD-MSCs seem to be able to sense and respond to the local environment. Even though a combination of different molecules may be involved in AD-MSC effects, the COX-2/PGE 2 pathway may play a role, suggesting that AD-MSCs may be useful for therapies in osteoarticular diseases.Osteoarthritis (OA) is a chronic age-related disease of the "whole joint" characterized by the slowly progressive destruction of articular cartilage accompanied by changes to synovium and subchondral bone, degeneration of ligaments and menisci, and hypertrophy of the joint capsule (1). In vivo and in vitro studies indicate that proinflammatory cytokines (interleukin-1␤ [IL-1␤], tumor necrosis factor ␣ [TNF␣], and IL-6) and chemokines (CXCL1/growth-related oncogene ␣ [GRO␣], CXCL8/IL-8, CCL2/monocyte chemotactic protein 1 , and CCL5/RANTES) produced by synoviocytes and chondrocytes, as well as cells from

Rehmannia glutinosa oligosaccharide induces differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells

“…Recent data show that MSCs also have immunomodulatory functions (Uccelli et al, 2006;Ramasamy et al, 2008), mainly through the release of soluble cytokines such as prostaglandin E2 (Manferdini et al, 2013), transforming growth factor b, human leukocyte antigen G5, and matrix metalloproteinase (De Miguel et al, 2012). Following transplantation, upregulation of CD4 + /CD25…”

Microvesicles from Human Adipose Tissue-Derived Mesenchymal Stem Cells as a New Protective Strategy in Osteoarthritic Chondrocytes

“…There is evidence that MSC secrete into their microenvironment a number of cytokines and growth factors that regulate intracellular signaling pathways in neighboring cells, promote angiogenesis and recruitment of stem/progenitor cells, or exert trophic and immunomodulatory effects (reviewed in [8]). As a result, treatment of OA chondrocytes or synovial cells with conditioned medium (CM) from bone marrow MSC or AD-MSC in an inflammatory environment can inhibit the production of inflammatory and catabolic agents [9, 10]. …”

Adipose derived stem cells for regenerative therapy in osteoarticular diseases

“…ASCs, even if derived from three different sources (Hoffa fat or subcutaneous hip or subcutaneous abdominal adipose tissue), induced the release of trophic factors that exerted anti-inflammatory effects (down expression of IL-1β, IL-6 and CXCL8/IL-8) on both synoviocytes and chondrocytes so corroborating their potential use in preventing OA progression [39]. The complexity of this anti-inflammatory effect may be due to a combination of different molecules, however the COX2/PGE2 pathway might be one of the modulators that plays a role in mechanism of action [39]. Furthermore, ASC in co-culture with OA chondrocytes significantly reduced the expression of TIMP-3 and MMP-13.…”