Improvement of survival of skin flaps by combined gene transfer of hepatocyte growth factor and prostacyclin synthase

Aya Nakagawa, Hirofumi Makino, Motokuni Aoki, Takashi Miyake, Suguru Shiraya, Toshikazu Nakamura, Toshio Ogihara, Yoshihiro Kimata, Ryuichi Morishita

Research output: Contribution to journalArticle

14 Citations (Scopus)

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. Methods and results: A 2 × 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 μg 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.

Original languageEnglish
Pages (from-to)1087-1094
Number of pages8
JournalJournal of Gene Medicine
Volume9
Issue number12
DOIs
Publication statusPublished - Dec 2007

Fingerprint

Hepatocyte Growth Factor
Skin
Transfection
Genes
Plasmids
prostacyclin synthetase
Angiogenesis Inducing Agents
Microvessels
varespladib methyl
Vasodilation
Needles
Therapeutics
Injections
DNA

Keywords

  • Angiogenesis
  • Gene therapy
  • Hepatocyte growth factor (HGF)
  • Prostacyclin
  • Skin flap

ASJC Scopus subject areas

  • Genetics

Cite this

Nakagawa, A., Makino, H., Aoki, M., Miyake, T., Shiraya, S., Nakamura, T., ... Morishita, R. (2007). Improvement of survival of skin flaps by combined gene transfer of hepatocyte growth factor and prostacyclin synthase. Journal of Gene Medicine, 9(12), 1087-1094. https://doi.org/10.1002/jgm.1105

Improvement of survival of skin flaps by combined gene transfer of hepatocyte growth factor and prostacyclin synthase. / Nakagawa, Aya; Makino, Hirofumi; Aoki, Motokuni; Miyake, Takashi; Shiraya, Suguru; Nakamura, Toshikazu; Ogihara, Toshio; Kimata, Yoshihiro; Morishita, Ryuichi.

In: Journal of Gene Medicine, Vol. 9, No. 12, 12.2007, p. 1087-1094.

Research output: Contribution to journalArticle

Nakagawa, A, Makino, H, Aoki, M, Miyake, T, Shiraya, S, Nakamura, T, Ogihara, T, Kimata, Y & Morishita, R 2007, 'Improvement of survival of skin flaps by combined gene transfer of hepatocyte growth factor and prostacyclin synthase', Journal of Gene Medicine, vol. 9, no. 12, pp. 1087-1094. https://doi.org/10.1002/jgm.1105
Nakagawa, Aya ; Makino, Hirofumi ; Aoki, Motokuni ; Miyake, Takashi ; Shiraya, Suguru ; Nakamura, Toshikazu ; Ogihara, Toshio ; Kimata, Yoshihiro ; Morishita, Ryuichi. / Improvement of survival of skin flaps by combined gene transfer of hepatocyte growth factor and prostacyclin synthase. In: Journal of Gene Medicine. 2007 ; Vol. 9, No. 12. pp. 1087-1094.
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