title: Endoluminal gingival fibroblast transfer reduces the size of rabbit carotid aneurisms via elastin repair.
abstract: OBJECTIVE
  Matrix metalloproteinase-9 is considered to play a pivotal role in aneurismal formation. We showed that gingival fibroblasts (GF) in vitro reduced matrix metalloproteinase-9 activity via increased secretion of tissue inhibitor of metalloproteinase 1. We aimed to evaluate in vivo the efficacy of GF transplantation to reduce aneurism development in a rabbit model.
  
  
  RESULTS
  Seventy rabbit carotid aneurisms were induced by elastase infusion. Four weeks later, GF, dermal fibroblast, or culture medium (DMEM) were infused into established aneurisms. Viable GF were abundantly detected in the transplanted arteries 3 months after seeding. GF engraftment resulted in a significant reduction of carotid aneurisms (decrease of 23.3% [P<0.001] and 17.6% [P=0.01] of vessel diameter in GF-treated arteries, 1 and 3 months after cell therapy, respectively), whereas vessel diameter of control DMEM and dermal fibroblast-treated arteries increased. GF inhibited matrix metalloproteinase-9 activity by tissue inhibitor of metalloproteinase 1 overexpression and matrix metalloproteinase-9/tissue inhibitor of metalloproteinase 1 complex formation, induced elastin repair, and increased elastin density in the media compared with DMEM-treated arteries (38.2 versus 18.0%; P=0.02). Elastin network GF-induced repair was inhibited by tissue inhibitor of metalloproteinase 1 blocking peptide.
  
  
  CONCLUSIONS
  Our results demonstrate that GF transplantation results in significant aneurism reduction and elastin repair. This strategy may be attractive because GF are accessible and remain viable within the grafted tissue.
authors.affiliation: Université Paris Descartes, INSERM, Assistance Publique-Hôpitaux de Paris, Laboratoire de Recherche Bio-Chirurgicale Fondation Alain Carpentier, Paris, France. eric.durand@egp.aphp.fr
authors.forename: Eric
authors.initials: E
authors.lastname: Durand
authors.forename: Benjamin
authors.initials: B
authors.lastname: Fournier
authors.forename: Ludovic
authors.initials: L
authors.lastname: Couty
authors.forename: Mathilde
authors.initials: M
authors.lastname: Lemitre
authors.forename: Paul
authors.initials: P
authors.lastname: Achouh
authors.forename: Pierre
authors.initials: P
authors.lastname: Julia
authors.forename: Ludovic
authors.initials: L
authors.lastname: Trinquart
authors.forename: Jean Noel
authors.initials: JN
authors.lastname: Fabiani
authors.forename: Sylvie
authors.initials: S
authors.lastname: Seguier
authors.forename: Bruno
authors.initials: B
authors.lastname: Gogly
authors.forename: Bernard
authors.initials: B
authors.lastname: Coulomb
authors.forename: Antoine
authors.initials: A
authors.lastname: Lafont
mesh_terms: D000783:Aneurysm / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D002340:Carotid Artery Diseases / Q000378:metabolism / Q000628:therapy*; D002470:Cell Survival; D002478:Cells, Cultured; D004549:Elastin / Q000502:physiology*; D005347:Fibroblasts / Q000637:transplantation*; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D011817:Rabbits; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D004549:Elastin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9