title: Intra-articular administration of xenogeneic neonatal Mesenchymal Stromal Cells early after meniscal injury down-regulates metalloproteinase gene expression in synovium and prevents cartilage degradation in a rabbit model of osteoarthritis.
abstract: OBJECTIVE
  The anti-inflammatory and anti-catabolic effects of neonatal Mesenchymal Stromal Cell (MSC) were investigated in a xenogeneic model of mild osteoarthritis (OA). The paracrine properties of MSC on synoviocytes were further investigated in vitro.
  
  
  METHODS
  OA was induced by medial meniscal release (MMR) in 30 rabbit knees. A single early (day 3) or delayed (day 15) intra-articular (IA) injection of MSC isolated from equine Umbilical Cord Wharton's jelly (UC-MSC) was performed. Rabbits were euthanized on days 15 or 56. OA grading was performed and gene expression of inflammatory cytokines and metalloproteinases was measured in synovial tissue. Paracrine effects of UC-MSC were investigated using UC-conditioned vs control medium on rabbit primary synoviocytes stimulated with interleukin 1 beta in vitro.
  
  
  RESULTS
  No adverse local or systemic responses were observed clinically after xenogeneic UC-MSC injection. At study end point, cartilage fibrillation was lower in early treatment than in delayed treatment group. Cellular infiltrate was observed in the synovium of both UC-MSC groups. OA synovium exhibited a reduced expression of metalloproteinases-1, -3, -13 in the early cell-treated group at d56. In vitro, UC-conditioned medium exerted anti-inflammatory and anti-catabolic effects on synoviocytes exposed to pro-inflammatory stimulus.
  
  
  CONCLUSIONS
  Early IA injection of equine UC-MSC was effective in preventing OA signs in rabbit knees following MMR. UC-MSC target the synovium and modulate the gene expression pattern of synoviocytes to promote an anti-catabolic environment. This confirms the synovium is a major target and mediator of MSC therapy, modulating the expression of matrix-degrading enzymes.
authors.affiliation: Vetbiobank, Marcy l'Etoile, France.
authors.forename: N
authors.initials: N
authors.lastname: Saulnier
authors.affiliation: UPSP 2011.03.101, VetAgro Sup, University of Lyon, Marcy l'Etoile, France.
authors.forename: E
authors.initials: E
authors.lastname: Viguier
authors.affiliation: CNRS UMR 5305, IBCP, Institut de Biologie et Chimie des Protéines, Lyon, France.
authors.forename: E
authors.initials: E
authors.lastname: Perrier-Groult
authors.affiliation: UPSP 2011.03.101, VetAgro Sup, University of Lyon, Marcy l'Etoile, France.
authors.forename: C
authors.initials: C
authors.lastname: Chenu
authors.affiliation: UPSP 2011.03.101, VetAgro Sup, University of Lyon, Marcy l'Etoile, France.
authors.forename: E
authors.initials: E
authors.lastname: Pillet
authors.affiliation: UPSP 2011.03.101, VetAgro Sup, University of Lyon, Marcy l'Etoile, France.
authors.forename: T
authors.initials: T
authors.lastname: Roger
authors.affiliation: Vetbiobank, Marcy l'Etoile, France.
authors.forename: S
authors.initials: S
authors.lastname: Maddens
authors.affiliation: UPSP 2011.03.101, VetAgro Sup, University of Lyon, Marcy l'Etoile, France. Electronic address: caroline.boulocher@vetagro-sup.fr.
authors.forename: C
authors.initials: C
authors.lastname: Boulocher
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D007270:Injections, Intra-Articular; D008592:Menisci, Tibial / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D045726:Metalloproteases / Q000235:genetics*; D010003:Osteoarthritis / Q000201:enzymology* / Q000517:prevention & control*; D011817:Rabbits; D013583:Synovial Membrane / Q000201:enzymology*; D000070600:Tibial Meniscus Injuries; D013997:Time Factors
chemical_list: D045726:Metalloproteases
keywords: Anti-catabolic effects; Osteoarthritis; Paracrine effects; Synovium; Umbilical cord-derived mesenchymal stromal cells; Xenogeneic