title: Gene therapy using hepatocyte growth factor expressing adenovirus improves skin flap survival in a rat model.
abstract: Hepatocyte growth factor (HGF) is a potent angiogenic factor that can stimulate the production of blood vessels in ischemic tissue. We investigated whether gene therapy using HGF-expressing adenovirus could enhance skin flap survival. Sprague-Dawley rats were randomly divided into three groups. Rats were subdermally injected with HGF-expressing adenovirus (HGF virus group), recombinant HGF (rhHGF group), or phosphate buffered saline (PBS group) 2 days before and immediately after 3 × 9 cm caudal flap elevation. The survival area of the skin flap, the ratio of blood flow, CD31-positive vessels and, VEGF expression were examined. Skin flap viability was significantly increased in the HGF virus group compared to the rhHGF and PBS groups (71.4% ± 5.9%, 63.8%± 6.4%, and 39.2% ± 13.0%, respectively) (P = 0.025). Furthermore, the blood flow ratio was significantly increased in the HGF virus group. In the HGF virus group, the number of CD31-positive vessels and vascular endothelial growth factor (VEGF) expression were significantly increased. Gene therapy using HGF-expressing adenovirus increase VEGF expression, the number of viable capillaries, and blood flow to the flap, thereby improving skin flap survival.
authors.affiliation: Institute for Human Tissue Restoration, Department of Plastic & Reconstructive Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Dong Kyun
authors.identifier: 0000-0002-4013-1131
authors.initials: DK
authors.lastname: Rah
authors.affiliation: Department of Plastic & Reconstructive Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: In Sik
authors.identifier: 0000-0003-1103-7047
authors.initials: IS
authors.lastname: Yun
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Korea.
authors.forename: Chae-Ok
authors.identifier: 0000-0002-9466-4531
authors.initials: CO
authors.lastname: Yun
authors.affiliation: Institute for Human Tissue Restoration, Department of Plastic & Reconstructive Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sae Bin
authors.identifier: 0000-0001-9456-0022
authors.initials: SB
authors.lastname: Lee
authors.affiliation: Institute for Human Tissue Restoration, Department of Plastic & Reconstructive Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Won Jai
authors.identifier: 0000-0003-3056-0503
authors.initials: WJ
authors.lastname: Lee
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D006085:Graft Survival / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000235:genetics*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019651:Plastic Surgery Procedures; D016038:Skin Transplantation / Q000379:methods*; D013524:Surgical Flaps / Q000601:surgery*
chemical_list: D017228:Hepatocyte Growth Factor
keywords: Adenovirus; Gene Therapy; Hepatocyte Growth Factor; Skin Flap