title: Reestablishment of the endothelial lining by endothelial cell therapy stabilizes experimental abdominal aortic aneurysms.
abstract: BACKGROUND
  Loss of the endothelium and its replacement by a thick thrombus are structural features of human abdominal aortic aneurysms (AAAs). In AAAs, the relationship between aortic diameter expansion, the presence of thrombus, and the lack of endothelial cells (ECs) remains unexplored. We hypothesized that reendothelialization by cell therapy would modulate aortic wall destruction and ultimately stabilize AAAs. We evaluated the impact of local seeding of rat aortic ECs or peripheral blood-derived outgrowth ECs on AAA evolution.
  
  
  RESULTS
  Rat aortic ECs (n=30) or serum-free medium (controls; n=29) were seeded endovascularly immediately (day 0) or 14 days after surgery in the rat xenograft model. Rat aortic EC seeding prevented AAA formation and stabilized formed AAAs at 28 days (diameter increase at day 0+28, 51±6% versus 83±6%; day 14+28, -1±4% versus 22±6% in rat aortic ECs and controls, respectively; P<0.01). This stabilizing effect was associated with the reestablishment of the endothelial lining, the suspension of proteolysis, and the reconstitution of new aortic wall rich in smooth muscle cells and extracellular matrix. Transplanted rat aortic ECs did not participate directly in aortic wall repair but exerted their healing properties through paracrine mechanisms involving the upregulation of endothelium-derived stabilizing factors and the recruitment of resident vascular cells. In rats, the transplantation of outgrowth ECs (n=7) significantly reduced by 30% the progression of AAAs and restored the abluminal endothelium at 28 days compared with controls (n=9).
  
  
  CONCLUSIONS
  Our study demonstrates the potential of restoring the endothelial lining to control AAA dynamics and designates ECs as an efficient therapy to stop AAA expansion.
authors.affiliation: CNRS EAC 7054, Centre de Recherches Chirurgicales Dominique Chopin, Faculty of Medicine, 8 rue du Général Sarrail, 94010 Créteil, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Franck
authors.forename: Jianping
authors.initials: J
authors.lastname: Dai
authors.forename: Alexandre
authors.initials: A
authors.lastname: Fifre
authors.forename: Saravuth
authors.initials: S
authors.lastname: Ngo
authors.forename: Claire
authors.initials: C
authors.lastname: Justine
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Michineau
authors.forename: Eric
authors.initials: E
authors.lastname: Allaire
authors.forename: Marianne
authors.initials: M
authors.lastname: Gervais
mesh_terms: D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000473:pathology / Q000601:surgery*; D017690:Cell Transplantation / Q000379:methods* / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology / Q000637:transplantation* / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000502:physiology / Q000637:transplantation* / Q000648:ultrastructure; D006168:Guinea Pigs; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014183:Transplantation, Heterologous / Q000379:methods
keywords: aortic aneurysm, abdominal; cell transplantation; endothelial cells; endothelium