title: Aging and diabetes impair the neovascular potential of adipose-derived stromal cells.
abstract: BACKGROUND
  Aging and diabetes are major risk factors for poor wound healing and tissue regeneration that reflect an impaired ability to respond to ischemic insults. The authors explored the intrinsic neovascular potential of adipose-derived stromal cells in the setting of advanced age and in type 1 and type 2 diabetes.
  
  
  METHODS
  Adipose-derived stromal cells isolated from young, aged, streptozotocin-induced, and db/db diabetic mice were exposed to normoxia and hypoxia in vitro. Vascular endothelial growth factor (VEGF) expression, proliferation, and tubulization were measured. Conditioned media harvested from adipose-derived stromal cell cultures were assessed for their ability to stimulate human umbilical vein endothelial cell proliferation (n = 3 and n = 3).
  
  
  RESULTS
  Young adipose-derived stromal cells demonstrated significantly higher levels of VEGF production, proliferation, and tubulogenesis than those derived from aged, streptozotocin-induced, and db/db mice in both normoxia and hypoxia. Although aged and diabetic adipose-derived stromal cells retained the ability to up-regulate VEGF secretion, proliferation, and tubulogenesis in response to hypoxia, the response was blunted compared with young controls. Conditioned media derived from these cells cultured in normoxia in vitro also had a significantly greater ability to increase human umbilical vein endothelial cell proliferation compared with media harvested from aged, streptozotocin-induced, and db/db adipose-derived stromal cells. This effect was magnified in conditioned media harvested from hypoxic adipose-derived stromal cell cultures.
  
  
  CONCLUSIONS
  This study demonstrates that aging and type 1 and type 2 diabetes impair intrinsic adipose-derived stromal cell function; however, these cells may still be a suitable source of angiogenic cells that can potentially improve neovascularization of ischemic tissues.
authors.affiliation: Stanford, Calif. From the Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine.
authors.forename: Samyra
authors.initials: S
authors.lastname: El-Ftesi
authors.forename: Edward I
authors.initials: EI
authors.lastname: Chang
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Gurtner
mesh_terms: D000273:Adipose Tissue / Q000098:blood supply / Q000166:cytology; D000375:Aging / Q000502:physiology*; D000818:Animals; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology*; D042783:Endothelial Cells / Q000166:cytology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018919:Neovascularization, Physiologic / Q000502:physiology*; D054411:Receptors, Leptin / Q000235:genetics*; D017154:Stromal Cells / Q000166:cytology*; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D054411:Receptors, Leptin; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse