Recombinant AAV vector encoding human VEGF165 enhances wound healing.
Delivery of therapeutic genes represents an appealing possibility to accelerate healing of wounds that are otherwise difficult to treat, such as those in patients with metabolic disorders or infections. Experimental evidence indicates that in such conditions potentiation of neo-angiogenesis at the wound site might represent an important therapeutic target. Here we explore the efficacy of gene therapy of wound healing with an adeno-associated virus (AAV) vector expressing the 165 amino acid isoform of vascular endothelial growth factor-A (VEGF-A). By gene marker studies, we found that AAV vectors are highly efficient for gene transfer to the rat skin, displaying an exquisite tropism for the panniculus carnosus. Gene expression from these vectors is sustained and persistent over time. Delivery of VEGF165 to full thickness excisional wounds in rats resulted in remarkable induction of new vessel formation, with consequent reduction of the healing time. Histological examination of treated wounds revealed accelerated remodeling of epidermis and dermis, with formation of a thick granular layer, containing numerous newly formed capillaries, as well as vessels of larger size. These data underline the importance of neo-angiogenesis in the healing process and indicate that VEGF gene transfer might represent a novel approach to treat wound healing disorders.
Deodato
B
B
Molecular Medicine Laboratory, International Center for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.
Arsic
N
N
Zentilin
L
L
Galeano
M
M
Santoro
D
D
Torre
V
V
Altavilla
D
D
Valdembri
D
D
Bussolino
F
F
Squadrito
F
F
Giacca
M
M
D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D016228:Endothelial Growth Factors / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D008222:Lymphokines / Q000235:genetics*; D008297:Male; D018919:Neovascularization, Physiologic; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000098:blood supply / Q000293:injuries*; D014161:Transduction, Genetic; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014945:Wound Healing
D016228:Endothelial Growth Factors; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors