Application of AAV2-mediated bFGF gene therapy on survival of ischemic flaps: effects of timing of gene transfer.
Necrosis of surgically transferred flaps is a major problem in reconstructive surgery. We investigated efficacy of a new vector system-adeno-associated viral 2 (AAV2)-mediated bFGF gene transfer to enhance survival of the ischemic flap. Thirty-eight Sprague-Dawley rats were divided into 3 gene therapy groups and 1 nontreated control of 9 or 10 each. 7.5 x 10(10) AAV2-bFGF viral particles were injected to the dorsum of each of the 29 rats; these rats were divided into 3 groups according to the timing of flap elevation. At the time of surgery, 1 week, and 2 weeks after surgery, flaps of 3 x 7 cm were raised. One week after surgery, flap viability was measured. Vascularization and immunohistochemical staining of the bFGF were evaluated of histologic sections. Flap viability was significantly improved by the AAV2-bFGF gene therapy at the time of surgery, and the flaps with the greatest survival area were found in the rats injected with AAV2-bFGF, 2 weeks before surgery. However, flap viability was significantly decreased by the gene therapy 1 week before surgery. Histologically, vascularity was increased in the groups with AAV2-bFGF injection and immunohistochemical staining showed greatly enhanced bFGF expression by gene transfer. The novel approach of AAV2-bFGF gene therapy shows encouraging manifestations in improving survival of flaps when the flaps are prefabricated during or 2 weeks before surgery.
Liu
Paul Y
PY
Department of Surgery, Roger Williams Medical Center, Boston University School of Medicine, Providence, RI, USA. pliu@rwmc.org
Wang
Xiao Tian
XT
Xin
Ke-Qin
KQ
Chen
Chuan Hao
CH
Rieger-Christ
Kimberley
K
Summerhayes
Ian C
IC
Wu
Ya Fang
YF
Tang
Jin Bo
JB
D000818:Animals; D000229:Dependovirus; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D007511:Ischemia / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013524:Surgical Flaps / Q000098:blood supply*; D013997:Time Factors
D016222:Fibroblast Growth Factor 2