title: Role of endothelial progenitor cells and inflammatory cytokines in healing of diabetic foot ulcers.
abstract: BACKGROUND
  To evaluate changes in endothelial progenitor cells (EPCs) and cytokines in patients with diabetic foot ulceration (DFU) in association with wound healing.
  
  
  METHODS
  We studied healthy subjects, diabetic patients not at risk of DFU, at risk of DFU and with active DFU. We prospectively followed the DFU patients over a 12-week period. We also investigated similar changes in diabetic rabbit and mouse models of wound healing.
  
  
  RESULTS
  All EPC phenotypes except the kinase insert domain receptor (KDR)(+)CD133(+) were reduced in the at risk and the DFU groups compared to the controls. There were no major EPC differences between the control and not at risk group, and between the at risk and DFU groups. Serum stromal-cell derived factor-1 (SDF-1) and stem cell factor (SCF) were increased in DFU patients. DFU patients who healed their ulcers had lower CD34(+)KDR(+) count at visits 3 and 4, serum c-reactive protein (CRP) and granulocyte-macrophage colony-stimulating factor (GM-CSF) at visit 1, interleukin-1 (IL-1) at visits 1 and 4. EPCs tended to be higher in both diabetic animal models when compared to their non-diabetic counterparts both before and ten days after wounding.
  
  
  CONCLUSIONS
  Uncomplicated diabetes does not affect EPCs. EPCs are reduced in patients at risk or with DFU while complete wound healing is associated with CD34(+)KDR(+) reduction, suggesting possible increased homing. Low baseline CRP, IL-1α and GM-CSF serum levels were associated with complete wound healing and may potentially serve as prognostic markers of DFU healing. No animal model alone is representative of the human condition, indicating the need for multiple experimental models.
authors.affiliation: Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Francesco
authors.initials: F
authors.lastname: Tecilazich
authors.affiliation: Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Thanh
authors.initials: T
authors.lastname: Dinh
authors.affiliation: Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Leena
authors.initials: L
authors.lastname: Pradhan-Nabzdyk
authors.affiliation: Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Ermelindo
authors.initials: E
authors.lastname: Leal
authors.affiliation: Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America ; Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Tellechea
authors.affiliation: Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Antonios
authors.initials: A
authors.lastname: Kafanas
authors.affiliation: Technological Educational Institute of Messolonghi, Messolonghi, Greece.
authors.forename: Charalambos
authors.initials: C
authors.lastname: Gnardellis
authors.affiliation: Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Magargee
authors.affiliation: Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Andre
authors.initials: A
authors.lastname: Dejam
authors.affiliation: Flow Cytometry Core Facility, Beth Israel Deaconess Medical Center and Harvard Stem Cell Institute, Boston, Massachusetts, United States of America.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Toxavidis
authors.affiliation: Flow Cytometry Core Facility, Beth Israel Deaconess Medical Center and Harvard Stem Cell Institute, Boston, Massachusetts, United States of America.
authors.forename: John C
authors.initials: JC
authors.lastname: Tigges
authors.affiliation: Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Carvalho
authors.affiliation: Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Lyons
authors.affiliation: Microcirculation Laboratory and Joslin-Beth Israel Deaconess Foot Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Aristidis
authors.initials: A
authors.lastname: Veves
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D017719:Diabetic Foot / Q000503:physiopathology*; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011817:Rabbits; D013234:Stem Cells / Q000502:physiology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators