title: Diabetes impairs endothelial progenitor cell-mediated blood vessel formation in response to hypoxia.
abstract: BACKGROUND
  Diabetics suffer from vascular dysfunction with increased risks of coronary artery disease and peripheral vascular disease secondary to an impaired ability to respond to tissue ischemia. Because endothelial progenitor cells are known to home to sites of ischemia and participate in new blood vessel growth, the authors examined the effects of diabetes on human endothelial progenitor cell function and peripheral tissue signaling in hypoxia, and determined whether these cells might be a useful cell-based therapy for diabetic vascular complications.
  
  
  METHODS
  Circulating human endothelial progenitor cells from type 2 diabetic patients and controls were isolated and subjected to in vitro adhesion, migration, and proliferation assays (n = 5). Cell mobilization and recruitment were studied in vivo in diabetic and nondiabetic environments (n = 6). Exogenous human diabetic and normal cells were analyzed for therapeutic efficacy in a murine ischemia model (n = 6).
  
  
  RESULTS
  Adhesion, migration, and proliferation of human diabetic endothelial progenitor cells in response to hypoxia was significantly reduced compared with controls. In diabetic mice, cell mobilization from the bone marrow and recruitment into ischemic tissue was significantly reduced compared with controls. Normal cells injected systemically as replacement therapy in a diabetic mouse increased but did not normalize ischemic tissue survival.
  
  
  CONCLUSIONS
  These findings suggest that diabetes causes defects in both the endothelial progenitor cell and peripheral tissue responses to hypoxia. These changes in endothelial progenitor cell function and signaling offer a novel explanation for the poor clinical outcome of type 2 diabetics following ischemic events. Based on these findings, it is unlikely that endothelial progenitor cell-based cellular therapies will be able to prevent diabetic complications.
authors.affiliation: New York, N.Y.; and Stanford, Calif. From the Laboratory of Microvascular Research and Vascular Tissue Engineering, Institute of Reconstructive Plastic Surgery, New York University Medical Center; and Department of Surgery, Stanford University.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Capla
authors.forename: Raymon H
authors.initials: RH
authors.lastname: Grogan
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Callaghan
authors.forename: Robert D
authors.initials: RD
authors.lastname: Galiano
authors.forename: Oren M
authors.initials: OM
authors.lastname: Tepper
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Ceradini
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Gurtner
mesh_terms: D000368:Aged; D002448:Cell Adhesion; D015687:Cell Hypoxia; D002465:Cell Movement; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D018919:Neovascularization, Physiologic; D013234:Stem Cells / Q000502:physiology*