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Improvement of survival of skin flaps by combined gene transfer of hepatocyte growth factor and prostacyclin synthase
Author(s) -
Nakagawa Aya,
Makino Hirofumi,
Aoki Motokuni,
Miyake Takashi,
Shiraya Suguru,
Nakamura Toshikazu,
Ogihara Toshio,
Kimata Yoshihiro,
Morishita Ryuichi
Publication year - 2007
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1105
Subject(s) - transfection , hepatocyte growth factor , angiogenesis , prostacyclin , genetic enhancement , medicine , vascular endothelial growth factor , blood flow , vasodilation , surgery , gene , biology , cancer research , biochemistry , vegf receptors , receptor
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. Copyright © 2007 John Wiley & Sons, Ltd.