title: Electroporation-mediated HGF gene transfection protected the kidney against graft injury.
abstract: The annual rate of kidney graft loss caused by chronic allograft nephropathy (CAN) has not improved over the past decade. Recent reports suggest that acute renal ischemia results in development of CAN. The goal of the present study was to assess the renoprotective potential and safety of hepatocyte growth factor (HGF) gene transfer using a porcine kidney transplant warm ischemia injury model. Following left porcine kidney removal, 10 min of warm ischemic injury was intentionally induced. Next, the HGF expression vector or vehicle was infused into the renal artery with the renal vein clamped ex vivo, and electric pulses were discharged using bathtub-type electrodes. Kidney grafts were then transplanted after removing the right kidney. Histopathological examination of vehicle-transfected kidney transplant revealed initial tubular injury followed by tubulointerstitial fibrosis. In contrast, HGF-transfected kidneys showed no initial tubular damage and no interstitial fibrosis at 6 months post-transplant. We conclude that electroporation-mediated ex vivo HGF gene transfection protects the kidney against graft injury in a porcine model.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Isaka
authors.forename: K
authors.initials: K
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Takabatake
authors.forename: M
authors.initials: M
authors.lastname: Mizui
authors.forename: M
authors.initials: M
authors.lastname: Miura-Tsujie
authors.forename: N
authors.initials: N
authors.lastname: Ichimaru
authors.forename: K
authors.initials: K
authors.lastname: Yazawa
authors.forename: R
authors.initials: R
authors.lastname: Utsugi
authors.forename: A
authors.initials: A
authors.lastname: Okuyama
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: E
authors.initials: E
authors.lastname: Imai
authors.forename: S
authors.initials: S
authors.lastname: Takahara
mesh_terms: D000818:Animals; D018274:Electroporation / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D007262:Infusions, Intravenous; D007431:Intraoperative Complications / Q000628:therapy; D007511:Ischemia / Q000473:pathology / Q000628:therapy*; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D016030:Kidney Transplantation / Q000379:methods*; D012077:Renal Artery; D013552:Swine; D013556:Swine, Miniature; D014184:Transplantation, Homologous
chemical_list: D017228:Hepatocyte Growth Factor