title: Increase in vascular permeability and vasodilation are critical for proangiogenic effects of stem cell therapy.
abstract: BACKGROUND
  Proangiogenic cell therapy based on administration of bone marrow-derived mononuclear cells (BMCs) or endothelial progenitor cells (EPCs) is now under investigation in humans for the treatment of ischemic diseases. However, mechanisms leading to the beneficial effects of BMCs and EPCs remain unclear.
  
  
  RESULTS
  BMC- and CD34+-derived progenitor cells interacted with ischemic femoral arteries through SDF-1 and CXCR4 signaling and released nitric oxide (NO) via an endothelial nitric oxide synthase (eNOS)-dependent pathway. BMC-induced NO production promoted a marked vasodilation and disrupted vascular endothelial-cadherin/beta-catenin complexes, leading to increased vascular permeability. NO-dependent vasodilation and hyperpermeability were critical for BMC infiltration in ischemic tissues and their proangiogenic potential in a model of hindlimb ischemia in mice.
  
  
  CONCLUSIONS
  Our results propose a new concept that proangiogenic progenitor cell activity does not rely only on their ability to differentiate into endothelial cells but rather on their capacity to modulate the function of preexisting vessels.
authors.affiliation: Cardiovascular Research Center, INSERM U689, Hopital Lariboisière, 41 boulevard de la chapelle, 75475 Paris Cedex 10, France.
authors.forename: Dong
authors.initials: D
authors.lastname: You
authors.forename: Ludovic
authors.initials: L
authors.lastname: Waeckel
authors.forename: Téni G
authors.initials: TG
authors.lastname: Ebrahimian
authors.forename: Olivier
authors.initials: O
authors.lastname: Blanc-Brude
authors.forename: Philippe
authors.initials: P
authors.lastname: Foubert
authors.forename: Véronique
authors.initials: V
authors.lastname: Barateau
authors.forename: Micheline
authors.initials: M
authors.lastname: Duriez
authors.forename: Sophie
authors.initials: S
authors.lastname: Lericousse-Roussanne
authors.forename: José
authors.initials: J
authors.lastname: Vilar
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Dejana
authors.forename: Gérard
authors.initials: G
authors.lastname: Tobelem
authors.forename: Bernard I
authors.initials: BI
authors.lastname: Lévy
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Silvestre
mesh_terms: D000818:Animals; D001158:Arteries / Q000473:pathology; D001854:Bone Marrow Cells; D002199:Capillary Permeability; D042783:Endothelial Cells; D006614:Hindlimb; D007511:Ischemia / Q000628:therapy*; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D009569:Nitric Oxide / Q000378:metabolism; D033581:Stem Cell Transplantation / Q000379:methods*; D014664:Vasodilation
chemical_list: D009569:Nitric Oxide