Inhibition of stromal cell-derived factor-1α further impairs diabetic wound healing

J Vasc Surg. 2011 Mar;53(3):774-84. doi: 10.1016/j.jvs.2010.10.056. Epub 2011 Jan 6.


Objective: Impaired diabetic wound healing is associated with abnormal stromal cell-derived factor (SDF)-1α production, decreased angiogenesis, and chronic inflammation. Lentiviral-mediated overexpression of SDF-1α can correct the impairments in angiogenesis and healing in diabetic wounds. We hypothesized that SDF-1α is a critical component of the normal wound-healing response and that inhibition of SDF-1α would further delay the wound-healing process.

Methods: dB/Db diabetic mice and Db/+ nondiabetic mice were wounded with an 8-mm punch biopsy and the wounds treated with a lentiviral vector containing either the green fluorescent protein (GFP) or SDF-1α inhibitor transgene. The inhibitor transgene is a mutant form of SDF-1α that binds, but does not activate, the CXCR4 receptor. Computerized planimetry was used to measure wound size daily. Wounds were analyzed at 3 and 7 days by histology and for production of inflammatory markers using real-time polymerase chain reaction. The effect of the SDF-1α inhibitor on cellular migration was also assessed.

Results: Inhibition of SDF-1α resulted in a significant decrease in the rate of diabetic wound healing, (3.8 vs 6.5 cm(2)/day in GFP-treated wounds; P = .04), and also impaired the early phase of nondiabetic wound healing. SDF-1α inhibition resulted in fewer small-caliber vessels, less granulation tissue formation, and increased proinflammatory gene expression of interleukin-6 and macrophage inflammatory protein-2 in the diabetic wounds.

Conclusions: The relative level of SDF-1α in the wound plays a key role in the wound-healing response. Alterations in the wound level of SDF-1α, as seen in diabetes or by SDF-1α inhibition, impair healing by decreasing cellular migration and angiogenesis, leading to increased production of inflammatory cytokines and inflammation. Inhibition of SDF-1α further impairs diabetic wound healing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Movement
  • Chemokine CXCL12 / biosynthesis*
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL2 / genetics
  • Diabetes Complications / genetics
  • Diabetes Complications / metabolism*
  • Diabetes Complications / pathology
  • Diabetes Complications / physiopathology
  • Disease Models, Animal
  • Genetic Vectors
  • Granulation Tissue / metabolism
  • Granulation Tissue / pathology
  • Immunohistochemistry
  • Inflammation Mediators / metabolism
  • Interleukin-6 / genetics
  • Lentivirus / genetics
  • Mice
  • Mutation
  • Neovascularization, Physiologic
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Receptors, CXCR4 / metabolism
  • Time Factors
  • Wound Healing*


  • CXCR4 protein, mouse
  • Chemokine CXCL12
  • Chemokine CXCL2
  • Cxcl12 protein, mouse
  • Cxcl2 protein, mouse
  • Inflammation Mediators
  • Interleukin-6
  • RNA, Messenger
  • Receptors, CXCR4