Intramuscular E-selectin/adeno-associated virus gene therapy promotes wound healing in an ischemic mouse model

Punam P. Parikh, Roberta M. Lassance-Soares, Hongwei Shao, Manuela M. Regueiro, Yan Li, Zhao Jun Liu, Omaida C. Velazquez

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Poor wound healing in critical limb ischemia (CLI) is attributed to impaired neovascularization and reperfusion. Optimizing the ischemic wound with adhesion molecules that enhance stem cell homing may revolutionize treatment. The purpose of this study is to test the efficacy of adhesion molecule E-selectin on wound healing in an ischemic mouse wound. Methods: Adult FVB/NJ mice underwent unilateral femoral artery and vein ligation to induce CLI. A 4-mm punch biopsy wound was created on the anterior thigh to simulate ischemic wounds. Intramuscular injection of adeno-associated virus (AAV) carrying either E-selectin (E-selectin/AAV, n = 11) or LacZ as control (LacZ/AAV, n = 10) was performed. Gross wound size was measured for 10 d postoperatively. Ischemic hindlimb reperfusion was quantified using laser Doppler imaging. Wound tissue neovascularization was visualized using DiI perfusion and confocal microscopy. E-selectin expression in wounds was verified by immunofluorescence. Results: Immunofluorescence confirmed E-selectin/AAV delivery in treatment versus control limbs. Wounds from E-selectin/AAV mice versus controls revealed surface area healing of 54% versus 20% (P < 0.01) on postoperative day (POD) 1, 78% versus 51% on POD 4 (P < 0.01), and 97% versus 84% on POD 10 (P < 0.01). Laser Doppler imaging revealed greater reperfusion in E-selectin/AAV mice versus controls by POD 10 (0.49 versus 0.27, P < 0.05). DiI perfused ligated hindlimb in E-selectin/AAV versus control mice revealed mean neovascularization intensity score of 30 versus 18 (P < 0.05) on POD 10. Conclusions: Intramuscularly injected E-selectin/AAV gene therapy in mice with CLI significantly increases wound angiogenesis and limb reperfusion, expediting overall wound healing.

Original languageEnglish (US)
Pages (from-to)68-76
Number of pages9
JournalJournal of Surgical Research
Volume228
DOIs
StatePublished - Aug 2018

Keywords

  • Gene therapy
  • Limb ischemia
  • Wound healing

ASJC Scopus subject areas

  • Surgery

Fingerprint Dive into the research topics of 'Intramuscular E-selectin/adeno-associated virus gene therapy promotes wound healing in an ischemic mouse model'. Together they form a unique fingerprint.

Cite this