title: Lack of anti-inflammatory and anti-catabolic effects on basal inflamed osteoarthritic chondrocytes or synoviocytes by adipose stem cell-conditioned medium.
abstract: OBJECTIVE
  To define whether good manufacturing practice (GMP)-clinical grade adipose stem cell (ASC)-derived conditioned medium (CM) is as effective as GMP-ASC in modulating inflammatory and catabolic factors released by both osteoarthritis (OA) chondrocytes or synoviocytes.
  
  
  METHODS
  OA chondrocytes and synoviocytes were treated with ASC-CM or co-cultured with ASC. Inflammatory factors (IL6, CXCL1/GROα,CXCL8/IL8, CCL2/MCP-1, CCL3/MIP-1α and CCL5/RANTES) and proteinases, such as metalloproteinase (MMP13), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS4, ADAMTS5) and their tissue metalloproteinase inhibitors (TIMP1, TIMP3) were evaluated by qRT-PCR or immunoassays. The involvement of prostaglandin E2 (PGE2) was also analyzed.
  
  
  RESULTS
  Most ASC-CM ratios tested did not decrease IL6, CCL2/MCP-1, CCL3/MIP1-α, CCL5/RANTES on basal inflamed chondrocytes or synoviocytes in contrast to what we found using ASC in co-culture. CXCL8/IL8 and CXCL1/GROα were not decreased by ASC-CM on synoviocytes but were only partially reduced on chondrocytes. Moreover, ASC-CM was less efficient both on basal inflamed OA chondrocytes and synoviocytes in reducing proteinases, such as MMP13, ADAMTS4, ADAMTS5 and increasing TIMP1 and TIMP3 compared to ASC in co-culture. The different ratios of ASC-CM contain lower amounts of PGE2 which were not sufficient to reduce inflammatory factors.
  
  
  CONCLUSIONS
  These data show that ASC-CM has a limited ability to decrease inflammatory and proteinases factors produced by OA chondrocytes or synoviocytes. ASC-CM is not sufficient to recapitulate the beneficial effect demonstrated using ASC in co-culture with inflamed OA chondrocytes and synoviocytes and shows that their use in clinical trials is fundamental to counteract OA progression.
authors.affiliation: SC Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, Istituto Ortopedico Rizzoli, Bologna 40136, Italy; Laboratorio RAMSES, Istituto Ortopedico Rizzoli, Bologna 40136, Italy. Electronic address: cristina.manferdini@ior.it.
authors.forename: C
authors.initials: C
authors.lastname: Manferdini
authors.affiliation: Inserm U844, Hôpital Saint-Eloi, Montpellier F-34295, France; Université Montpellier 1, UFR de Médicine, Montpellier F-34967, France. Electronic address: marie.maumus@inserm.fr.
authors.forename: M
authors.initials: M
authors.lastname: Maumus
authors.affiliation: Laboratorio RAMSES, Istituto Ortopedico Rizzoli, Bologna 40136, Italy. Electronic address: elena.gabusi@ior.it.
authors.forename: E
authors.initials: E
authors.lastname: Gabusi
authors.affiliation: Laboratorio RAMSES, Istituto Ortopedico Rizzoli, Bologna 40136, Italy. Electronic address: francesca.paolella@ior.it.
authors.forename: F
authors.initials: F
authors.lastname: Paolella
authors.affiliation: Laboratorio RAMSES, Istituto Ortopedico Rizzoli, Bologna 40136, Italy. Electronic address: francesco.grassi@ior.it.
authors.forename: F
authors.initials: F
authors.lastname: Grassi
authors.affiliation: Inserm U844, Hôpital Saint-Eloi, Montpellier F-34295, France; Université Montpellier 1, UFR de Médicine, Montpellier F-34967, France; Service d'Immuno-Rhumatologie Thérapeutique, Hopital Lapeyronie, Montpellier F-34295, France. Electronic address: christian.jorgensen@inserm.fr.
authors.forename: C
authors.initials: C
authors.lastname: Jorgensen
authors.affiliation: EFS-Pyrénéés-Méditerranéé, Toulouse F-31300, France. Electronic address: sandrine.fleury@efs.sante.fr.
authors.forename: S
authors.initials: S
authors.lastname: Fleury-Cappellesso
authors.affiliation: Inserm U844, Hôpital Saint-Eloi, Montpellier F-34295, France; Université Montpellier 1, UFR de Médicine, Montpellier F-34967, France. Electronic address: daniele.noel@inserm.fr.
authors.forename: D
authors.initials: D
authors.lastname: Noël
authors.affiliation: SC Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, Istituto Ortopedico Rizzoli, Bologna 40136, Italy; Laboratorio RAMSES, Istituto Ortopedico Rizzoli, Bologna 40136, Italy. Electronic address: gina.lisignoli@ior.it.
authors.forename: G
authors.initials: G
authors.lastname: Lisignoli
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D000368:Aged; D002358:Cartilage, Articular / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology*; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
chemical_list: D017077:Culture Media, Conditioned
keywords: Adipose stem cells; Chondrocytes; Conditioned-medium; Osteoarthritis; Synoviocytes