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

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-s...

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Bibliographic Details
Published in:The Journal of surgical research 2018-08, Vol.228, p.68-76
Main Authors: Parikh, Punam P., Lassance-Soares, Roberta M., Shao, Hongwei, Regueiro, Manuela M., Li, Yan, Liu, Zhao-Jun, Velazquez, Omaida C.
Format: Article
Language:English
Subjects:
Animals
Dependovirus - genetics
Disease Models, Animal
E-Selectin - genetics
Gene therapy
Genetic Therapy - methods
Genetic Vectors - administration & dosage
Genetic Vectors - genetics
HEK293 Cells
Hindlimb - blood supply
Hindlimb - diagnostic imaging
Humans
Injections, Intramuscular
Ischemia - diagnostic imaging
Ischemia - genetics
Ischemia - therapy
Laser-Doppler Flowmetry
Limb ischemia
Male
Mice
Neovascularization, Physiologic - genetics
Regional Blood Flow - genetics
Skin - blood supply
Skin - diagnostic imaging
Wound healing
Wound Healing - genetics
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Summary: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. 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. 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 
ISSN:0022-4804
1095-8673
DOI:10.1016/j.jss.2018.02.061