PMID- 23613363 OWN - NLM STAT- MEDLINE DCOM- 20130618 LR - 20220321 IS - 1529-0131 (Electronic) IS - 0004-3591 (Linking) VI - 65 IP - 5 DP - 2013 May TI - Adipose-derived mesenchymal stem cells exert antiinflammatory effects on chondrocytes and synoviocytes from osteoarthritis patients through prostaglandin E2. PG - 1271-81 LID - 10.1002/art.37908 [doi] AB - OBJECTIVE: To examine the effect of different sources of good manufacturing practice clinical grade adipose-derived mesenchymal stem cells (AD-MSCs) on inflammatory factors in osteoarthritic (OA) chondrocytes and synoviocytes. METHODS: AD-MSCs from infrapatellar Hoffa fat, subcutaneous (SC) hip fat, and SC abdominal fat were cocultured in Transwells with chondrocytes or synoviocytes. Inflammatory factors (interleukin-1beta [IL-1beta], tumor necrosis factor alpha, IL-6, CXCL1/growth-related oncogene alpha, CXCL8/IL-8, CCL2/monocyte chemotactic protein 1, CCL3/macrophage inflammatory protein 1alpha, and CCL5/RANTES) were evaluated by quantitative reverse transcription-polymerase chain reaction or multiplex bead-based immunoassay. The role of different immunomodulators was analyzed. 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 down-modulation 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 E2 (PGE2 ) pathway exerted a role in the mechanism of antiinflammatory AD-MSC action. CONCLUSION: The antiinflammatory effects of AD-MSCs 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/PGE2 pathway may play a role, suggesting that AD-MSCs may be useful for therapies in osteoarticular diseases. CI - Copyright (c) 2013 by the American College of Rheumatology. FAU - Manferdini, Cristina AU - Manferdini C AD - Istituto Ortopedico Rizzoli, Bologna, Italy. FAU - Maumus, Marie AU - Maumus M FAU - Gabusi, Elena AU - Gabusi E FAU - Piacentini, Anna AU - Piacentini A FAU - Filardo, Giuseppe AU - Filardo G FAU - Peyrafitte, Julie-Anne AU - Peyrafitte JA FAU - Jorgensen, Christian AU - Jorgensen C FAU - Bourin, Philippe AU - Bourin P FAU - Fleury-Cappellesso, Sandrine AU - Fleury-Cappellesso S FAU - Facchini, Andrea AU - Facchini A FAU - Noel, Daniele AU - Noel D FAU - Lisignoli, Gina AU - Lisignoli G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Arthritis Rheum JT - Arthritis and rheumatism JID - 0370605 RN - 0 (Biomarkers) RN - 0 (Chemokines) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Adipocytes/*cytology MH - Aged MH - Biomarkers/metabolism MH - Cartilage, Articular/pathology MH - Cells, Cultured MH - Chemokines/genetics/metabolism MH - Chondrocytes/*cytology/metabolism MH - Coculture Techniques MH - Dinoprostone/*metabolism MH - Down-Regulation MH - Female MH - Gene Expression Regulation MH - Humans MH - Male MH - Mesenchymal Stem Cells/*cytology/metabolism MH - Osteoarthritis/*pathology MH - Synovial Membrane/*cytology/metabolism EDAT- 2013/04/25 06:00 MHDA- 2013/06/19 06:00 CRDT- 2013/04/25 06:00 PHST- 2012/09/17 00:00 [received] PHST- 2013/02/12 00:00 [accepted] PHST- 2013/04/25 06:00 [entrez] PHST- 2013/04/25 06:00 [pubmed] PHST- 2013/06/19 06:00 [medline] AID - 10.1002/art.37908 [doi] PST - ppublish SO - Arthritis Rheum. 2013 May;65(5):1271-81. doi: 10.1002/art.37908.