title: Utility of a Mouse Model of Osteoarthritis to Demonstrate Cartilage Protection by IFNγ-Primed Equine Mesenchymal Stem Cells.
abstract: OBJECTIVE
  Mesenchymal stem cells isolated from adipose tissue (ASC) have been shown to influence the course of osteoarthritis (OA) in different animal models and are promising in veterinary medicine for horses involved in competitive sport. The aim of this study was to characterize equine ASCs (eASCs) and investigate the role of interferon-gamma (IFNγ)-priming on their therapeutic effect in a murine model of OA, which could be relevant to equine OA.
  
  
  METHODS
  ASC were isolated from subcutaneous fat. Expression of specific markers was tested by cytometry and RT-qPCR. Differentiation potential was evaluated by histology and RT-qPCR. For functional assays, naïve or IFNγ-primed eASCs were cocultured with peripheral blood mononuclear cells or articular cartilage explants. Finally, the therapeutic effect of eASCs was tested in the model of collagenase-induced OA (CIOA) in mice.
  
  
  RESULTS
  The immunosuppressive function of eASCs on equine T cell proliferation and their chondroprotective effect on equine cartilage explants were demonstratedin vitro. Both cartilage degradation and T cell activation were reduced by naïve and IFNγ-primed eASCs, but IFNγ-priming enhanced these functions. In CIOA, intra-articular injection of eASCs prevented articular cartilage from degradation and IFNγ-primed eASCs were more potent than naïve cells. This effect was related to the modulation of eASC secretome by IFNγ-priming.
  
  
  CONCLUSIONS
  IFNγ-priming of eASCs potentiated their antiproliferative and chondroprotective functions. We demonstrated that the immunocompetent mouse model of CIOA was relevant to test the therapeutic efficacy of xenogeneic eASCs for OA and confirmed that IFNγ-primed eASCs may have a therapeutic value for musculoskeletal diseases in veterinary medicine.
authors.affiliation: U1183, INSERM, Hôpital Saint-Eloi, Montpellier, France; Montpellier University, UFR de Médecine, Montpellier, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Maumus
authors.affiliation: Sanofi , Montpellier , France.
authors.forename: Gautier
authors.initials: G
authors.lastname: Roussignol
authors.affiliation: U1183, INSERM, Hôpital Saint-Eloi, Montpellier, France; Montpellier University, UFR de Médecine, Montpellier, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Toupet
authors.affiliation: Sanofi , Montpellier , France.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Penarier
authors.affiliation: Sanofi , Montpellier , France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bentz
authors.affiliation: Sanofi , Montpellier , France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Teixeira
authors.affiliation: Sanofi , Montpellier , France.
authors.forename: Didier
authors.initials: D
authors.lastname: Oustric
authors.affiliation: Sanofi , Montpellier , France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Jung
authors.affiliation: GREMERES-ICE, University of Lyon , Marcy l'Etoile , France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lepage
authors.affiliation: Sanofi , Montpellier , France.
authors.forename: Regis
authors.initials: R
authors.lastname: Steinberg
authors.affiliation: U1183, INSERM, Hôpital Saint-Eloi, Montpellier, France; Montpellier University, UFR de Médecine, Montpellier, France; Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Hôpital Lapeyronie, Montpellier, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Jorgensen
authors.affiliation: U1183, INSERM, Hôpital Saint-Eloi, Montpellier, France; Montpellier University, UFR de Médecine, Montpellier, France; Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Hôpital Lapeyronie, Montpellier, France.
authors.forename: Danièle
authors.initials: D
authors.lastname: Noel
keywords: cartilage; cell therapy; horse; mesenchymal stem cells; osteoarthritis; secretome