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2004 Fiscal Year Final Research Report Summary

Suppression of hepatic ischemia/reperfusion injury by early expression of protective protein

Research Project

Project/Area Number 15591404
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionOsaka University

Principal Investigator

UMESHITA Koji  Osaka University, Hospital, Assistant Professor, 医学部附属病院, 助手 (60252649)

Co-Investigator(Kenkyū-buntansha) KANEDA Yasufumi  Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (10177537)
NAGANO Hiroaki  Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 講師 (10294050)
Project Period (FY) 2003 – 2004
KeywordsLiver / ischemia-reperfusion / transplantation / gene therapy / RNA / electroporation / HVJ Envelope Vector
Research Abstract

In the first year of the study period, we succeeded in stable synthesis and amplification of mRNA using mCAP RNA Capping Kit. Next, we moved to in vitro mRNA transfer study using HVJ Envelope VECTOR KIT and got 500- to 1000-fold increase in luciferase assay in BHK21 cells compared with control. When HVJ envelope vector containing luciferase mRNA was injected to the liver via portal vein in C57BL/6 mice in vivo, 5- to 10-fold increase was obtained. In the second year, we injected mRNA to the liver via portal vein in Wistar rats at 4C ex vivo using the same method. However, only 2- to 3-fold increase was observed in luciferase assay. We, therefore, tried ultrasound-mediated gene transfer with echo contrast microbubble (Optison), which has recently been shown to be highly efficient, in stead of HVJ envelope vector. In the preliminary experiment using luciferase reporter gene, luciferase activity of liver graft 24 hours after transfection and syngeneic transplantation was significantly increased about 17-fold as compared with plasmid infusion alone. When vascular clamping was performed together, additional 10-fold increase was obtained. In the next step, mRNA transfer into liver graft using ultrasound-mediated method would be performed.

  • Research Products

    (10 results)

All 2005 2004 2003

All Journal Article (10 results)

  • [Journal Article] Nonviral gene transfer of human hepatocyte growth factor improves streptozotocin-induced diabetic neuropathy in rats2005

    • Author(s)
      Kato, N., Kaneda, Y, et al.
    • Journal Title

      Diabetes 54

      Pages: 846-854

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Nonviral gene transfer of human hepatocyte growth factor improves streptozotocin-induced diabetic neuropathy in rats.2005

    • Author(s)
      Kato, N., Nemoto, K., Nakanishi, K., Morishita, R., Kaneda, Y., Uenoyama, M., Ikeda, T., Fujikawa, K.
    • Journal Title

      Diabetes 54

      Pages: 846-854

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A novel therapeutic strategy to treat brain ischemia : Over-expression of hepatocyte growth factor gene reduced ischemic injury without cerebral edema in rat model2004

    • Author(s)
      Shimamura, M., Kaneda, Y, et al.
    • Journal Title

      Circulation 109

      Pages: 424-431

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cytoprotection by bcl-2 gene transfer against ischemic liver injuries together with repressed lipid peroxidation and increased ascorbic acid in livers and serum.2004

    • Author(s)
      Yanada, S., Kaneda, Y, et al.
    • Journal Title

      J Cell Biochem 93

      Pages: 857-870

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Safety evaluation of clinical gene therapy using hepatocyte growth factor to treat peripheral arterial disease2004

    • Author(s)
      Morishita, R., Kaneda, Y, et al.
    • Journal Title

      Hypertension 44

      Pages: 203-209

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A novel therapeutic strategy to treat brain ischemia : Over-expression of hepatocyte growth factor gene reduced ischemic injury without cerebral edema in rat model.2004

    • Author(s)
      Shimamura, M., Sato, N., Oshima, K., Aoki, M., Kurinami, H., Waguri, S., Uchiyama, Y., Ogihara, T., Kaneda, Y., Morishita, R.
    • Journal Title

      Circulation 109

      Pages: 424-431

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cytoprotection by bcl-2 gene transfer against ischemic liver injuries together with repressed lipid peroxidation and increased ascorbic acid in livers and serum.2004

    • Author(s)
      Yanada, S., Saitoh, Y., Kaneda, Y., Miwa, N.
    • Journal Title

      J Cell Biochem 93

      Pages: 857-870

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Safety evaluation of clinical gene therapy using hepatocyte growth factor to treat peripheral arterial disease.2004

    • Author(s)
      Morishita, R., Aoki, M., Hashiya, N., Makino, H., Yamasaki, K., Azuma, J., Sawa, Y, Matsuda, H., Kaneda, Y., Ogihara, T.
    • Journal Title

      Hypertension 44

      Pages: 203-209

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Electroporation-mediated ex vivo gene transfer into graft not requiring injection pressure in orthotopic liver transplantation2003

    • Author(s)
      Kobayashi S., Umeshita K, et al.
    • Journal Title

      J Gene Med 5(6)

      Pages: 510-517

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Electroporation-mediated ex vivo gene transfer into graft not requiring injection pressure in orthotopic liver transplantation.2003

    • Author(s)
      Kobayashi S., Dono S., (Takahara S.), (Isaka Y.), (Imai E.), (Zhenhui L.), Nagano H., Kato T., Umeshita K., Nakamori S., Sakon M., Monden M.
    • Journal Title

      J Gene Med 5(6)

      Pages: 510-517

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2006-07-11  

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