title: Augmentation of transgene expression in cold-preserved organs using vascular endothelial growth factor receptor-mediated adenoviral vector combined with hyperbaric oxygen.
abstract: Adenovirus-mediated gene transfer has been widely used in gene therapy for congenital metabolic, cardiovascular, and malignant diseases. It has been reported that a gene transfer technique into transplanted organs may suppress rejection reactions and inhibit preservation injury. However, the magnitude of transgene expression in organs preserved at a cold temperature remains to be determined. In this study, we compared the transgene expression using vascular endothelial growth factor receptor (VEGFR)-mediated adenoviral vector at cold versus warm temperatures alone and combined with hyperbaric oxygen in cold-preserved organs. The transgene expression by porcine endothelial cells transduced with adenoviral vector was significantly higher after a 24 hour-incubation at warm temperature than after a 1 hour-incubation with warm or cold temperature. Moreover, the transgene expression of after a 1-hour incubation at cold temperature was significantly lower than a 1-hour incubation at warm temperature. The VEGFR-mediated adenoviral vector augmented transgene expression during a 1-hour incubation at cold temperature compared to the control vector. A/J skin graft survival in C3H mice was significantly prolonged compared to control or standard vector with CTLA4Ig cDNA using VEGFR-mediated adenoviral vector with CTLA4Ig cDNA in a 1-hour cold preservation. Furthermore, combined use of VEGFR-mediated adenoviral vector with CTLA4Ig cDNA plus FK506 showed an augmented effect on graft prolongation. It is concluded that adenovirus-mediated gene transfer in 1-hour cold-preserved organ is difficult compared to that in the warm condition. However, VEGFR-mediated gene transfer can augment the transgene expression in 1-hour cold-preserved organs, followed by the effective suppression of rejection reactions in allogeneic transplantation.
authors.affiliation: Department of Surgery, National East Nagoya Hospital, Nagoya, Aichi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hayashi
authors.forename: D-K
authors.initials: DK
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Yagi
authors.forename: H
authors.initials: H
authors.lastname: Takagi
authors.forename: A
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000069594:Abatacept; D000256:Adenoviridae; D000818:Animals; D030801:Animals, Genetically Modified; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003110:Colonic Neoplasms; D004730:Endothelium, Vascular / Q000502:physiology*; D005822:Genetic Vectors; D006084:Graft Rejection; D006931:Hyperbaric Oxygenation; D018796:Immunoconjugates / Q000235:genetics; D051379:Mice; D008805:Mice, Inbred A; D008809:Mice, Inbred C3H; D009926:Organ Preservation; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics*; D016038:Skin Transplantation / Q000276:immunology; D013552:Swine; D014184:Transplantation, Homologous
chemical_list: D018796:Immunoconjugates; D000069594:Abatacept; D040262:Receptors, Vascular Endothelial Growth Factor