title: Adipose-derived mesenchymal stem cells exert antiinflammatory effects on chondrocytes and synoviocytes from osteoarthritis patients through prostaglandin E2.
abstract: 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-1β [IL-1β], tumor necrosis factor α, IL-6, CXCL1/growth-related oncogene α, CXCL8/IL-8, CCL2/monocyte chemotactic protein 1, CCL3/macrophage inflammatory protein 1α, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Istituto Ortopedico Rizzoli, Bologna, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Manferdini
authors.forename: Marie
authors.initials: M
authors.lastname: Maumus
authors.forename: Elena
authors.initials: E
authors.lastname: Gabusi
authors.forename: Anna
authors.initials: A
authors.lastname: Piacentini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Filardo
authors.forename: Julie-Anne
authors.initials: JA
authors.lastname: Peyrafitte
authors.forename: Christian
authors.initials: C
authors.lastname: Jorgensen
authors.forename: Philippe
authors.initials: P
authors.lastname: Bourin
authors.forename: Sandrine
authors.initials: S
authors.lastname: Fleury-Cappellesso
authors.forename: Andrea
authors.initials: A
authors.lastname: Facchini
authors.forename: Danièle
authors.initials: D
authors.lastname: Noël
authors.forename: Gina
authors.initials: G
authors.lastname: Lisignoli
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002358:Cartilage, Articular / Q000473:pathology; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D018920:Coculture Techniques; D015232:Dinoprostone / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010003:Osteoarthritis / Q000473:pathology*; D013583:Synovial Membrane / Q000166:cytology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018925:Chemokines; D015232:Dinoprostone