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Novel tissue regeneration using polymer nano-micelle gene delivery system

Research Project

Project/Area Number 16390506
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Plastic surgery
Research InstitutionThe University of Tokyo

Principal Investigator

TAKATO Tsuyoshi  The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (90171454)

Co-Investigator(Kenkyū-buntansha) CHIKAZU Daichi  The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (30343122)
HOSHI Kazuto  The University of Tokyo, Faculty of Medicine, Visiting Assistant Professor, 医学部附属病院, 寄附講座教員 (30344451)
KOYAMA Hiroyuki  The University of Tokyo, Faculty of Medicine, Visiting Assistant Professor, 医学部附属病院, 寄附講座教員 (10241994)
NISHIYAMA Nobuhiro  The University of Tokyo, Faculty of Medicine, Assistant, 大学院・医学系研究科, 助手 (10372385)
KATAOKA Kazunori  The University of Tokyo, Faculty of Medicine, Professor, 大学院・医学系研究科, 教授 (00130245)
江口 智明  東京大学, 医学部附属病院, 講師 (00302688)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2005: ¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 2004: ¥7,000,000 (Direct Cost: ¥7,000,000)
KeywordsPolymer nano-micellsb / Reverse transfection / collagen gel / Bone regeneration / Gene delivery / Vascular tissue / RGD / RGDペプチド / Artery wall binding peptide / Reverse transfect
Research Abstract

(1)Development of non-viral vector system for specific gene delivery
To develop nano-micelle gene vector for specific gene delivery, we added ligand peptides (RGD peptide, ring-formed RGD peptide or artery wall binding peptide) to the poly-ion complex nano-micelle system (RGD micelle, ring-RGD micelle and AWBP micelle). The evaluations using several culture cell lines showed that gene transfer efficiency by ring-RGD micelle was significantly higher than those by micelle without ligand and RGD micelle. Further, in culture smooth muscle cells, AWBP micelle showed remarkable gene transfer as compared with other micelles.
(2)Developmento of gene delivery method for vascularization of reconstructive tissue
Although we assessed in vivo gene delivery efficiency to muscle tissue by using RGD micelle and ring-RGD micelle, there was no significant advantage in RGD micelle and ring-RGD micelle as compared with non-ligand micelle. We also tested gene delivery effect by AWBP micelle to the injured arterial wall, but no significant effect was detected. Therefore, we established new gene transfer approach of nano-micelle gene vector by using reverse transfection method. Further, we also carried out the evaluation of new poly-ion micelle, PEG-DET, and observed favorable gene delivery to rabbit carotid artery.
(3)Vascularization of regenerative bone
PEG-DET containing three kinds of gene, which potentially stimulate bone regeneration, was implanted to mice with appropriate scaffold, and favorable bone regeneration was observed in the scaffold.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (20 results)

All 2006 2005 2004 Other

All Journal Article (20 results)

  • [Journal Article] Inflammatory responses involving tumor necrosis factor receptor-associated factor 6 contribute to in-stent lesion formation in a stent implantation model of rabbit carotid artery.2006

    • Author(s)
      Miyahara T, Takato T, et al.
    • Journal Title

      Journal of Vacular Surgery 43

      Pages: 592-600

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Inflammatory responses involving tumor necrosis factor receptor-associated factor 6 contribute to in-stent lesion formation in a stent implantation model of rabbit carotid artery.2006

    • Author(s)
      Miyahara T, Takato T, et al.
    • Journal Title

      Journal of Vascular Surgery 43

      Pages: 592-600

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Gene transfer of bFGF to recipient bed improves survival of ischemic skin flap.2005

    • Author(s)
      Fujihara Y, Takato T, et al.
    • Journal Title

      British Journal of Plastic Surgery, 58

      Pages: 511-517

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Total upper lip reconstruction after surgical resection of malignant melanoma.2005

    • Author(s)
      Eguchi T, Takato T, et al.
    • Journal Title

      Scand J Plast Reconstr Surg Hand 39

      Pages: 45-47

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner2005

    • Author(s)
      Yano F, Takato T, et al.
    • Journal Title

      Biochemical & Biophysical Research Communications. 333

      Pages: 1300-1308

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Molecular and pharmacological characteristics of transient voltage-dependent K+ currents in cultured human pulmonary arterial smooth muscle cells.2005

    • Author(s)
      Iida H, Takato T, et al.
    • Journal Title

      British Journal of Plastic Surgery, 146

      Pages: 49-59

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CpG island methylator phenotype is a determinant of poor prognosis in neuroblastomas2005

    • Author(s)
      Abe M, Takato T, et al.
    • Journal Title

      Cancer Research 65

      Pages: 828-834

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene transfer of bFGF to recipient bed improves survival of ischemic skin flap.2005

    • Author(s)
      Fujihara Y, Takato T, et al.
    • Journal Title

      British Journal of Plastic Surgery 58

      Pages: 511-517

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Total upper lip reconstruction after surgical resection of malignant melanoma.2005

    • Author(s)
      Eguchi T, Takato T et al.
    • Journal Title

      Scand J Plast Reconstr Surg Hand 39

      Pages: 45-47

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner2005

    • Author(s)
      Yano F., Takato T.et al.
    • Journal Title

      Biochemical & Biophysical Research Communications 333

      Pages: 1300-1308

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Molecular and pharmacological characteristics of transient voltage-dependent K+ currents in cultured human pulmonary arterial smooth muscle cells.2005

    • Author(s)
      Iida H., Takato T., et al.
    • Journal Title

      British Journal of Pharmacology 146

      Pages: 49-59

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] CpG island methylator phenotype is a strong determinant of poor prognosis in neuroblastomas2005

    • Author(s)
      Abe M., Takato T.et al.
    • Journal Title

      Cancer Research 65

      Pages: 828-834

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner2005

    • Author(s)
      Yano F., Takato T.et al.
    • Journal Title

      Biochemical & Biophysical Research Communications. 333

      Pages: 1300-1308

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Molecular and pharmacological characteristics of transient voltage-dependent K+ currents in cultured human pulmonary arterial smooth muscle cells.2005

    • Author(s)
      Iida H., Takato T.et al.
    • Journal Title

      British Journal of Pharmacology. 146

      Pages: 49-59

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Gelatin hydrogel microspheres enable pinpoint delivery of basic fibroblast growth factor for development of functional collateral vessels2004

    • Author(s)
      Hosaka A, Koyama H, Takato T et al.
    • Journal Title

      Circulation 110

      Pages: 3322-3328

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Inflammatory signaling pathway containing TRAF6 contributes to neointimal formation via diverse mechanisms.2004

    • Author(s)
      Miyahara T, Koyama H, Takato T et al.
    • Journal Title

      Cardiovascular Research 64

      Pages: 154-164

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Block catiomer polyplexes with regulated densities of charge and disulfide cross-linking directed to enhance gene expression.2004

    • Author(s)
      Miyata K, Koyama H, Kataoka K et al.
    • Journal Title

      Journal of American Chemical Society 126

      Pages: 2355-2361

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Conduction performance of collateral vessels induced by vascular endothelial growth factor or basic fibroblast growth factor.2004

    • Author(s)
      Kondoh K, Koyama H, Takato T et al.
    • Journal Title

      Cardiovascular Research 61

      Pages: 132-142

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gene transfer of bFGF to recipient bed improves survival of ischemic skin flap

    • Author(s)
      Fujihara Y, Koyama H, Eguchi T, Takato T
    • Journal Title

      British Journal of Plastic Surgery (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Total upper lip reconstruction after surgical resection of a malignant melanoma

    • Author(s)
      Eguchi T, Takato T et al.
    • Journal Title

      Scand J Plast Reconstr Surg Hand (In press)

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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