title: Improvement of survival of skin flaps by combined gene transfer of hepatocyte growth factor and prostacyclin synthase.
abstract: BACKGROUND
  Increasing the local blood flow is a critical factor for long-term survival of skin flaps. Thus, a molecular therapy to increase the blood flow by means of an angiogenic factor is considered to be a useful strategy to improve skin flap survival. We focused on a combined strategy to stimulate not only angiogenesis, but also vasodilation of local microvessels, using co-transfection of the hepatocyte growth factor (HGF) and prostacyclin synthase (PGIS) genes to enhance the survival of random-pattern skin flaps.
  
  
  RESULTS
  A 2 x 8 cm full thickness cranial pedicled random-pattern flap was made on the back of each 12-week-old male rat. At 3 days before operation, 400 microg of human HGF and PGIS naked plasmid DNA or control plasmid was transfected into the flaps by needle-less injection using a Shima Jet, resulting in successful expression of human HGF and PGIS in the skin flaps. Transfection of both genes into the distal half of skin flaps at 3 days prior to operation significantly increased the survival rate of skin flaps, while transfection all over the flaps did not. In addition, transfection prior to operation was more effective than simultaneous treatment. Moreover, co-transfection of these genes improved the survival area of skin flaps, accompanied by an increase in blood flow of skin flaps, even in a diabetic model.
  
  
  CONCLUSIONS
  Overall, these results indicate that combination treatment with HGF and PGIS genes by Shima Jet could be an effective strategy to improve skin flap survival.
authors: Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan.
authors: Aya
authors: A
authors: Nakagawa
authors: Hirofumi
authors: H
authors: Makino
authors: Motokuni
authors: M
authors: Aoki
authors: Takashi
authors: T
authors: Miyake
authors: Suguru
authors: S
authors: Shiraya
authors: Toshikazu
authors: T
authors: Nakamura
authors: Toshio
authors: T
authors: Ogihara
authors: Yoshihiro
authors: Y
authors: Kimata
authors: Ryuichi
authors: R
authors: Morishita
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D062109:Dermatologic Surgical Procedures; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013524:Surgical Flaps; D014162:Transfection
chemical_list: D017228:Hepatocyte Growth Factor; D003577:Cytochrome P-450 Enzyme System; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase