Gene transfer of bFGF to recipient bed improves survival of ischemic skin flap.
BACKGROUND
The recipient bed is a promising target of angiogenic therapy to treat ischemic skin flaps. We delivered basic fibroblast growth factor (bFGF) gene to the recipient bed by a plasmid-based method with electroporation, and assessed the effects on flap viability in a rat dorsal skin flap model.


METHODS
A 25 x 90 mm(2) axial skin flap was elevated on the back of male Sprague-Dawley rats. Two days before flap elevation, an expression plasmid vector containing the bFGF gene with the signal sequence was injected into the dorsal muscles beneath the skin flap, and then electroporation was delivered (FGF-E(+) group). As control, rats were injected with a plasmid vector containing LacZ gene (LacZ-E(+) group), instead of bFGF gene. Other groups of animals received plasmid vector containing bFGF (FGF-E(-) group) or LacZ (LacZ-E(-) group) gene without electroporation. Seven days later, the area of necrosis and neovascularisation of the skin flap were evaluated.


RESULTS
The bFGF gene was successfully transferred to the dorsal muscles, and bFGF was expressed in muscle tissue. The area of flap necrosis (%) in the FGF-E(+) group (21.7+/-5.3%) was significantly smaller than that in the LacZ-E(+) (28.3+/-4.1%), FGF-E(-) (29.7+/-3.3%), and LacZ-E(-) (28.1+/-2.5%) groups. Postmortem angiograms and histological analyses showed that vascularisation in the distal part of the skin flap was significantly increased in the FGF-E(+) group compared with the other groups.


CONCLUSIONS
These findings suggested that gene delivery of bFGF to the recipient bed muscles enhanced vascularity and viability of an ischemic skin flap, and that plasmid-based gene delivery with electroporation was a suitable delivery method.
Fujihara
Y
Y
Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Koyama
H
H
Nishiyama
N
N
Eguchi
T
T
Takato
T
T
D000818:Animals; D018274:Electroporation; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006085:Graft Survival; D007511:Ischemia / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008833:Microcirculation; D009336:Necrosis; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000098:blood supply* / Q000473:pathology; D016038:Skin Transplantation; D013524:Surgical Flaps / Q000098:blood supply / Q000473:pathology
D016222:Fibroblast Growth Factor 2