移植腎へのHGF遺伝子導入の臨床研究

• Project/Area Number: 15109009
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Urology
• Research Institution: Osaka University
• Principal Investigator: 奥山 明彦 大阪大学, 医学系研究科, 教授 (20093388)
• Co-Investigator(Kenkyū-buntansha): 高原 史郎 大阪大学, 医学系研究科, 寄附講座教授 (70179547) ; 今井 圓裕 大阪大学, 医学系研究科, 講師 (00223305)
• Project Period (FY): 2003 – 2005
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥39,130,000 (Direct Cost: ¥30,100,000、Indirect Cost: ¥9,030,000); Fiscal Year 2004: ¥29,250,000 (Direct Cost: ¥22,500,000、Indirect Cost: ¥6,750,000); Fiscal Year 2003: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
• Keywords: Hepatocyte Growth Factor / 遺伝子治療 / electropotation法 / 腎移植 / 慢性拒絶反応 / 線維化 / 大動物 / 長期生着 / 腎臓移植 / 臓器保存 / Hepatocyte Growth Facto / electroporation法

Research Abstract

研究実績の概要
(1)ブタ腎へのelectroporatign法によるHGF遺伝子直接導入(安全性試験):平成15年度報告に記載した安全性試験の結果を論文投稿し、追加実験(病理診断とPCR法による長期遺伝子発現の有無の確認)を要求され、実施した。再投稿し受理された(Gene Therapy : in press)
(2)ブタ腎へのHGF直接投与による有効性および安全性試験:大阪大学医学部附属病院・遺伝子治療臨床研究審査委員会から要求された追加実験有効性試験は終了。

Research Products

• [Journal Article] Comprehensive examination of gene expression associated with long-term stable graft acceptance (2004)
  • Author(s): H.Zhang
  • Journal Title: Clin Transplant 18 Pages: 70-78
• [Journal Article] Direct HGF gene transfer into kidney suppressed cyclosporine A nephropathy. (2004)
  • Author(s): Yazawa Y
  • Journal Title: Nephrol Dial Transplant 19 Pages: 1-5
• [Journal Article] Electroporation-mediated HGF gene transfer ameliorated cyclosporine nephrotoxicity. (2004)
  • Author(s): Mizui M
  • Journal Title: Kidney Int 65 Pages: 2041-2053
• [Journal Article] Activation of the signal transducer and activator of transcription signaling pathway in renal proximal tubular cells by albumin. (2004)
  • Author(s): Nakajima H
  • Journal Title: J Am Soc Nephrol 15 Pages: 276-285
• [Journal Article] Exploring RNA Interference as a Therapeutic Strategy for Renal Disease.
  • Author(s): Takabatake Y
  • Journal Title: Gene Therapy in press
• [Journal Article] Actions of a Rho Signaling Inhibitor, Y-27632, Against Progression in a Mouse Model of Hepatocellular Carcinoma
  • Author(s): F.Xue
  • Journal Title: Gastroenterology in press
• [Journal Article] Rapid recovery from liver injury in hepatectomized rat by naked HGF gene transfer
  • Author(s): Kobayashi, S
  • Journal Title: Hepatology in press
• [Journal Article] Electroporation-mediated HGF gene transfection protected the kidney against graft injury.
  • Author(s): Isaka, Y
  • Journal Title: Gene Therapy in press
• [Publications] S.Kobayashi, K.Dono, T.Tanaka, S.Takahara, et al.: "Gene transfer into the liver by plasmid injection into the portal vein combined with electroporation"J Gene Med. 5. 201-208 (2003)
• [Publications] F.Xue, T.Takahara, Y.Yata, Y.Kuwabara, E.Shinno, K.Nonome, M.Minemura, S.Takahara: "Hepatocyte growth factor gene therapy accelerates regeneration in cirrhotic mouse livers after hepatectomy"GUT. 52. 694-700 (2003)
• [Publications] K.Yazawa, Y.Isaka, S.Takahara, E.Imai, et al.: "Direct HGF gene transfer into kidney suppressed cyclosporine A nephropathy."Nephrol Dial Transplant. (In press). (2004)
• [Publications] S.Kobayashi, K.Dono, T.Tanaka, T.Kato, H.Nagano, K.Umeshita, et al.: "Rapid recovery from liver injury in hepatectomized rat by naked HGF gene transfer with in vivo electoroporation"Hepatology. (In press). (2004)