title: Lentiviral gene transfer of SDF-1alpha to wounds improves diabetic wound healing.
abstract: BACKGROUND
  Chronic wounds continue to be a major clinical problem and novel therapeutic approaches are needed. We have previously demonstrated that treatment of diabetic mouse wounds with local application of stromal progenitor cells results in improved healing and increased production of stromal-derived growth factor-1alpha (SDF-1alpha). We hypothesized that lentiviral-mediated increased production of SDF-1alpha in the wound environment could also improve diabetic wound healing.
  
  
  METHODS
  Full-thickness excisional wounds were created in Db-/Db- mice and immediately treated with 10(6), 10(8), or 10(9) plaque-forming units of a lentiviral construct containing GFP-SDF-1alpha or GFP alone. At 7 and 14 days post wounding, wounds were harvested for histological and molecular analysis.
  
  
  RESULTS
  At 7 days, Db-/Db- wounds treated with lenti GFP-SDF-1alpha exhibited a decrease in wound surface area for all doses tested. Morphologically, SDF-treated wounds were more cellular with increased granulation tissue volume compared to controls (P < 0.05). GFP expression was maintained in treated tissue at 7 days post wounding, but little expression was observed at 14 days. While we did not observe a difference in the gross wound surface area at 14 days, histological analysis revealed that SDF-treated wounds were fully epithelialized (n = 6) compared to only one of six controls.
  
  
  CONCLUSIONS
  Lentiviral-mediated overproduction of SDF-1alpha is sufficient to correct the pathophysiologic abnormalities in diabetic wound healing resulting in complete epithelialization at 2 weeks. SDF-1alpha-mediated improvement in diabetic wound healing has significant implications for the development of novel therapeutic strategies to facilitate wound closure which target progenitor cell mobilization and recruitment.
authors.affiliation: The Center for Fetal Research at The Children's Hospital of Philadelphia, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Andrea T
authors.initials: AT
authors.lastname: Badillo
authors.forename: Sophie
authors.initials: S
authors.lastname: Chung
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
authors.forename: Philip
authors.initials: P
authors.lastname: Zoltick
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Liechty
mesh_terms: D000818:Animals; D054377:Chemokine CXCL12 / Q000235:genetics* / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000378:metabolism*
chemical_list: D054377:Chemokine CXCL12; D012333:RNA, Messenger