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Non-invasive soft tissue reconstruction using therapeutic angiogenesis.

Research Project

Project/Area Number 15390536
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

EGUCHI Tomoaki  The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (00302688)

Co-Investigator(Kenkyū-buntansha) KOYAMA Hiroyuki  The University of Tokyo, Faculty of Medicine, Visiting Assistant Professor, 医学部附属病院, 客員助教授 (10241994)
CHIKAZU Daichi  The University of Tokyo, Faculty of Medicine, Research Assistant, 医学部附属病院, 助手 (30343122)
TAKATO Tsuyoshi  The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (90171454)
KATAOKA Kazunori  The University of Tokyo, Graduate School of Medicine, Professor, 大学院・工学系研究科, 教授 (00130245)
TABATA Yasuhiko  Kyoto University, Professor, 再生医科学研究所, 教授 (50211371)
荻原 祐二  東京大学, 医学部附属病院, 助手 (20345226)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥10,800,000 (Direct Cost: ¥10,800,000)
Fiscal Year 2004: ¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 2003: ¥5,700,000 (Direct Cost: ¥5,700,000)
KeywordsAcidic gelatin hydrogel / Micropheres / bFGF / Polymer micelle / Recipient bed / Axial skin flap / In vivo electroporation / Recipient bed / 塩基性線維芽細胞増殖因子 / 血管新生療法 / Skin flap / Electroporation / 高分子ミセル型ナノ・パーティクル
Research Abstract

1.Gene transfer of bFGF to recipient bed improves survival of ischemic skin flap.
Axial skin flap was elevated in the dorsum of rat. Two days before flap elevation, expression plasmid vector containing bFGF gene was injected to the dorsal muscles beneath the designed skin flap, and then electroporation was delivered (E-FGF group). Some rats were injected with plasmid vector containing LacZ gene (E-Cont group) as control. Seven days later, the size of flap necrosis in the E-FGF group was significantly smaller than that of E-cont group. Postmortem angiograms and histological analyses showed that the vascularization in the distal part of skin flap significantly increased in the E-FGF group as compared with control.
2.Controlled delivery of recombinant bFGF to recipient bed of ischemic skin flap.
Recombinant bFGF was delivered to recipient bed of rat axial skin flap, and its therapeutic effect was evaluated. Immediately after flap elevation, bFGF-impregnated acidic gelatin hydrogel microspheres were injected to the dorsal muscles beneath the designed skin flap (G-FGF group). Acidic gelatin hydrogel microsphere is a controlled release system of bFGF protein. Control rats received PBS-treated acidic gelatin hydrogel microspheres in the same manner (G-Cont group). Seven days later, flap neovascularization in the G-FGF group was significantly higher than that in the G-Cont group, and then the size of flap necrosis in the G-FGF group was significantly smaller than that of the G-Cont group.
3.Gene delivery with polymer micelle non-viral vector.
To establish non-viral gene delivery system for recipient bed of ischemic skin flap, nano-sized polymer micelle containing plasmid DNA was evaluated. However, polymer micelle vector showed no remarkable advantage in gene transfer efficiency to muscle tissue as compared with sole injection of naked plasmid.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (20 results)

All 2005 2004 Other

All Journal Article (17 results) Publications (3 results)

  • [Journal Article] Gene transfer of bFGF to recipient bed improves survival of isch emic skin flap.2005

    • Author(s)
      Fujihara Y, Koyama H, Eguchi T, Takto T
    • 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
      2004 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
      2004 Final Research Report Summary
  • [Journal Article] The canonical Wnt signaling pathway promotes chondrocyte differ entiation in a Sox9-dependent manner.2005

    • Author(s)
      Yano F, Takato T, Chung UI 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
      2004 Final Research Report Summary
  • [Journal Article] Gene transfer of bFGF to recipient bed improves survival of ischemic skin flap.2005

    • Author(s)
      Fujihara Y, Koyama H, Eguchi T, Takato T.
    • 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
      2004 Final Research Report Summary
  • [Journal Article] The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner.2005

    • Author(s)
      Yano F.Takato T.Chung UI 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
      2004 Final Research Report Summary
  • [Journal Article] Gelatin hydrogel microspheres enable pinpoint delivery of basic fibrobl ast growth factor for the development of functional collateral vessels.2004

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

      Circulation 110

      Pages: 3322-3328

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] THe combination of SOX5,SOX6, and SOX9 provides signals suffcient for induction of permanent cartilage.2004

    • Author(s)
      IKeda T, Takato T, Ikegawa S, Chung UI
    • Journal Title

      Arthristis & Rheumatism 50

      Pages: 3561-3573

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inflammatory signaling pathway containing TRAF6 contributes to neoinitimal formation via diverse mechanisms.2004

    • Author(s)
      Miyahara T, Koyama H, Inoue J, Takto T
    • Journal Title

      Cardiovascular Research 64

      Pages: 154-164

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Gelatin hydrogel microspheres enable pinpoint delivery of basic fibroblast growth factor for the development of functional collateral vessels.2004

    • Author(s)
      Hosaka A.Koyama H.Tabata N.Takato et al.
    • Journal Title

      Circulation 110

      Pages: 3322-3328

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The combination of SOX5, SOX6, and SOX9 provides signals sufficient for induction of permanent cartilage.2004

    • Author(s)
      Ikeda T.Takato T.Ikegawa S.Chung UI et al.
    • Journal Title

      Arthritis & Rheumatism. 50

      Pages: 3561-3573

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inflammatory signaling pathway containing TRAF6 contributes to neointimal formation via diverse mechanisms.2004

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

      Cardiovascular Research. 64

      Pages: 154-164

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Force defisit in neurovascular muscle transfer is partially explained by a denervated muscle fiber population2004

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

      Basic Appl Myol 14

      Pages: 179-189

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gelatin hydrogel microspheres enable pinpoint delivery of basic fibsroblast 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] 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] Absence of platelet-activating factor receptor protects mice from osteoporosis following ovariectomy.2004

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

      Journal of Clinical Investigation 114

      Pages: 85-93

    • 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 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
  • [Publications] Kondou K, Takato T et al.: "Conduction Performance of Collateral Vessels Induced by Vascular Endthelial Growth Factor or Basic Fibroblast Growth Factor"Cardiovascular Research. 61. 132-142 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishii S, Koyama H et al.: "Appropriate control of ex vivo gene therapy delivering basic fibroblast growth factor promotes successful and safe development of collateral vessels"Journal of Vascular Surgery. 39. 629-638 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishikage S, Koyama H et al.: "In vivo electroporation enhances plasmid-based gene transfer of basic fibroblast growth factor for the treatment of ischemic limb"Journal of Surgical Research. (In press). (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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