title: Human cord blood endothelial progenitors promote post-ischemic angiogenesis in immunocompetent mouse model.
abstract: BACKGROUND
  Human cord blood (CB) endothelial colony forming cells (ECFCs) are endowed with high vascular regenerative ability in immunodeficient mice, but their immunogenicity and susceptibility to rejection in immunocompetent models has yet to be explored.
  
  
  METHODS
  We injected CB ECFCs in non-immuno-suppressed C57BL/6J mice after having induced the hindlimb ischemia and we investigated their contribution to the recovery from the ischemic injury. Human ECFCs (hECFCs) were administered by intramuscular injection and hindlimb blood perfusion was measured by laser Doppler analysis at 7-day intervals for 28days after treatment. Mice were sacrificed after 7 and 28days and immunohistochemistry for specific human (CD31) and mouse (von Willebrand factor) endothelial antigens was carried out. Before euthanasia, blood samples to assess cytokines and angiogenic growth factor levels were collected.
  
  
  RESULTS
  Mice injected with hECFCs showed a prompter and greater recovery of blood flow than controls. Several endothelial cells of human origin were detected at day7 after injection and their number declined progressively. Likewise, a progressive increase of mouse-derived vascular structures were observed, paralleled by the amplified endogenous production of various soluble mediators of angiogenesis, including Vascular Endothelial Growth Factor and Fibroblast Growth Factor.
  
  
  CONCLUSIONS
  Overall, our findings are consistent with the hypothesis that human ECFCs might expand the endogenous vascular repair potential of recipients and support their possible HLA-independent unconventional use.
authors.affiliation: Department of Internal Medicine, Catholic University, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Flex
authors.affiliation: Department of Rheumatology, Catholic University, Rome, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Biscetti
authors.affiliation: Institute of Hematology, Catholic University, Rome, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Iachininoto
authors.affiliation: Institute of Hematology, Catholic University, Rome, Italy.
authors.forename: Eugenia Rosa
authors.initials: ER
authors.lastname: Nuzzolo
authors.affiliation: Institute of Hematology, Catholic University, Rome, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Orlando
authors.affiliation: Institute of Hematology, Catholic University, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Capodimonti
authors.affiliation: Department of Internal Medicine, Catholic University, Rome, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Angelini
authors.affiliation: Institute of Hematology, Catholic University, Rome, Italy.
authors.forename: Caterina Giovanna
authors.initials: CG
authors.lastname: Valentini
authors.affiliation: Institute of Hematology, Catholic University, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Bianchi
authors.affiliation: Department of Pathology, Catholic University, Rome, Italy.
authors.forename: Luigi Maria
authors.initials: LM
authors.lastname: Larocca
authors.affiliation: Department of Pathology, Catholic University, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Martini
authors.affiliation: Institute of Hematology, Catholic University, Rome, Italy. Electronic address: luciana.teofili@unicatt.it.
authors.forename: Luciana
authors.initials: L
authors.lastname: Teofili
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000637:transplantation*; D005312:Fetal Blood / Q000166:cytology*; D006614:Hindlimb / Q000098:blood supply* / Q000473:pathology; D006801:Humans; D007511:Ischemia / Q000097:blood / Q000473:pathology / Q000628:therapy*; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000098:blood supply / Q000473:pathology; D018919:Neovascularization, Physiologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D016207:Cytokines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014841:von Willebrand Factor
keywords: Angiogenic factors; Endothelial progenitor cells; Graft rejection; Immune tolerance; Ischemia