title: Bone morphogenetic proteins 2 and 4 are selectively expressed by late outgrowth endothelial progenitor cells and promote neoangiogenesis.
abstract: OBJECTIVE
  Endothelial progenitor cells are currently identified either by their surface antigen expression or by their generation of early colonies in culture (CFU-Hill). Another population, endothelial colony-forming cells (ECFCs), has strong vessel-forming capacity but is less well characterized. Given the potential usefulness of CFU-Hill and ECFCs as cell therapy products, their thorough characterization is of major importance.
  
  
  RESULTS
  CFU-Hill and ECFCs were expanded from human cord and adult blood. Bone morphogenetic proteins 2 and 4 (BMP2/4) were selectively expressed by ECFCs but not by CFU-Hill. The BMP pathway was involved in ECFC commitment and angiogenic potential in vitro. In vivo, BMP inhibition strongly reduced plug vascularization in bFGF-containing Matrigel plugs implanted in C57/Bl6 mice. Moreover, ECFC exposure to BMP increased their therapeutic potential in a nude mouse model of hindlimb ischemia. In amputation specimens from patients with critical leg ischemia who had received a local therapeutic injection of bone marrow mononuclear cells, newly formed vessels were strongly positive for BMP2/4, suggesting that endothelial cells involved in neovascularization have an ECFC-like phenotype.
  
  
  CONCLUSIONS
  BMP2/4 are a marker of ECFCs and play a key role in ECFC commitment and outgrowth during neovascularization.
authors.affiliation: Université Paris Descartes, Faculté de Pharmacie, INSERM UMRS 765, 4 Avenue de l'observatoire, F-75006 Paris, France.
authors.forename: David M
authors.initials: DM
authors.lastname: Smadja
authors.forename: Ivan
authors.initials: I
authors.lastname: Bièche
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Silvestre
authors.forename: Stéphane
authors.initials: S
authors.lastname: Germain
authors.forename: Adeline
authors.initials: A
authors.lastname: Cornet
authors.forename: Ingrid
authors.initials: I
authors.lastname: Laurendeau
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Duong-Van-Huyen
authors.forename: Joseph
authors.initials: J
authors.lastname: Emmerich
authors.forename: Michel
authors.initials: M
authors.lastname: Vidaud
authors.forename: Martine
authors.initials: M
authors.lastname: Aiach
authors.forename: Pascale
authors.initials: P
authors.lastname: Gaussem
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics*; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics*; D002352:Carrier Proteins / Q000494:pharmacology; D003114:Colony-Forming Units Assay; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism* / Q000637:transplantation; D005312:Fetal Blood / Q000166:cytology; D015870:Gene Expression; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007511:Ischemia / Q000235:genetics / Q000473:pathology / Q000628:therapy; D007866:Leg / Q000098:blood supply; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D000099176:Noggin Protein
chemical_list: D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D002352:Carrier Proteins; D000099176:Noggin Protein; C525718:BMP2 protein, human; C525809:BMP4 protein, human; C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse