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Application of newly-developed gene transfer to regeneration of bone and periodontal tissue

Research Project

Project/Area Number 16390579
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

KASUGAI Shohei  Tokyo Medical and Dental University, Graduate School, Prof, 大学院医歯学総合研究科, 教授 (70161049)

Co-Investigator(Kenkyū-buntansha) KONDO Hisatomo  Tokyo Medical and Dental University, Graduate School, Research Associate, 大学院医歯学総合研究科, 助手 (70343150)
KURODA Shinji  Tokyo Medical and Dental University, Dental Hospital, Research Associate, 歯学部附属病院, 助手 (50323689)
ASAHINA Izumi  Nagasaki University, Graduate School, Prof, 医歯薬学総合研究科, 教授 (30221039)
ODA Shigeru  Tokyo Medical and Dental University, Graduate School, Lecturer, 大学院医歯学総合研究科, 講師 (70160869)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2006: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2004: ¥6,300,000 (Direct Cost: ¥6,300,000)
KeywordsGene Transfer / Plasmid DNA / BMP / Bone / Periodontal tissue / Tissue Regeneration / Collagen / Ligament / プラスミドDNA / 再生医療
Research Abstract

As regenerative therapies for bone and periodontal tissues several methods have been developed and clinically applied ; however, a method, which is simple, safe and economical for public society, is required. Although gene transfer with plasmid DNA is safe and clinically applied, it is a problem that efficiency of this gene transfer is extremely low. In the present study, we obtained the following results.
1. When plasmid DNA was combined with small Ca-phosphate particles and transplanted to the tissue defect, the efficiency of gene transfer increased. Small Ca-phosphate particles bound plasmid DNA and kept it locally. Furthermore, the binding to the particles increased the resistance to DNase. These phenomena would contribute to the increase of gene transfer.
2. Utilizing this method, we applied plasmid DNA encoding human BMP2 to 5 mm segmental bone defects of rat tibias. Six weeks the defects completely healed and the mechanical strength of the bone was comparable to the normal tibia at 8 weeks. Although knot-like bone appeared at the applied site, it was gradually absorbed and the bone shape became normal.
3. Similarly, plasmid DNA encoding human BMP12 was applied to the bone defects of rat femurs. Ligament-like tissue abundant in collagen fibers was formed from the previous defect to the surrounding tissue whereas the defect was filled with bone. This method would be promising for ligament reconstruction.
4. Periosteum cells were cultured and these cells were transferred with BMP2 and/or VEGF gene, which were then transplanted to nude mice. When both genes were transferred, the largest amount of bone was formed.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (37 results)

All 2007 2006 2005 2004 Other

All Journal Article (34 results) Book (3 results)

  • [Journal Article] Histological and histomorphometrical comparative study of the degradation and osteoconductive characteristics of alpha- and beta-tricalcium phosphate (TCP) in block grafts.2007

    • Author(s)
      Yamada M, Shiota M, Yamashita Y, Kasugai S
    • Journal Title

      Journal of Biomedical Material Research 80(in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Bone increase in rat tibiae by local administration of amino-terminally truncated rhFGF-4(73-206).2007

    • Author(s)
      Kuroda S., Kondo H, Ohya K, Kasugai S
    • Journal Title

      Tissue Engineering (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Histological and histomorphometrical comparative study of the degradation and osteoconductive characteristics of alpha-and beta-tricalcium phosphate(TCP) in block grafts.2007

    • Author(s)
      Yamada M, Shiota M, Yamashita Y, Kasugai S
    • Journal Title

      Journal of Biomedical Material Research (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Bone increase in rat tibiae by local administration of amino-terminally truncated rhFGF-4(73-206).2007

    • Author(s)
      Kuroda S, Kondo H, Ohya K, Kasugai S
    • Journal Title

      Tissue Engineering (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Biodegradable process of alpha-TCP particles and new gone formation in a rabbit cranial defect model.2006

    • Author(s)
      Kihara H, Shiota M, Yamashita Y, Kasugai S
    • Journal Title

      Journal of Biomedical Material Research, Part B : Applied Biomaterials 79B

      Pages: 284-291

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Platelet separation from whole blood in an aqueous two-phase system with water-soluble polymers.2006

    • Author(s)
      Sumida E, Iwasaki Y, Akiyoshi K, Kasugai S
    • Journal Title

      Journal of Pharmacological Sciences 101(1)

      Pages: 91-97

    • NAID

      10018237509

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Bone regeneration by modified gene-activated matrix; Effectiveness in segmental tibial defects in rats.2006

    • Author(s)
      Endo M, Kuroda S, Kondo H, Maruoka Y, Ohya K, Kasugai S
    • Journal Title

      Journal of Tissue Engineering 12(3)

      Pages: 489-497

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 歯科における再生医療の歴史と展望.2006

    • Author(s)
      春日井昇平
    • Journal Title

      日本歯科先端技術研究会雑誌 12

      Pages: 193-196

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 閉経に伴う顎骨の変化と歯科インプラント治療.2006

    • Author(s)
      春日井昇平
    • Journal Title

      Clinical Calcium 16(2)

      Pages: 124-129

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Biodegradable process of alpha-TCP particles and new gone formation in a rabbit cranial defect model.2006

    • Author(s)
      Kihara H, Shiota M, Yamashita Y, Kasugai S.
    • Journal Title

      Journal of Biomedical Material Research, Part B : Applied Biomaterials 79B

      Pages: 284-291

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Platelet separation from whole blood in an aqueous two-phase system with water-soluble polymers.2006

    • Author(s)
      Sumida E, Iwasaki Y, Akiyoshi K, Kasugai S.
    • Journal Title

      Journal of Pharmacological Sciences 101(1)

      Pages: 91-97

    • NAID

      10018237509

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Bone regeneration by modified gene-activated matrix ; Effectiveness in segmental tibial defects in rats.2006

    • Author(s)
      Endo M, Kuroda S, Kondo H, Maruoka Y, Ohya K, Kasugai S.
    • Journal Title

      Journal of Tissue Engineering 12(3)

      Pages: 489-497

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Preliminary studies of in vivo and ex vivo implantations accompanied by transgenes.2006

    • Author(s)
      Kuroda S, Endo M, Samee M, Kondo H, Kasugai S.
    • Journal Title

      Proceeding of the Symposium of Tissue Engineering in Dental Field : From Bench to Clinic (Edited by Kasugai S)(Zenkodo)

      Pages: 24-28

    • NAID

      130004456578

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Biodegradable process of alpha-TCP particles and new gone formation in a rabbit cranial defect model.2006

    • Author(s)
      Kihara H, Shiota M, Yamashita Y, Kasugai S
    • Journal Title

      Journal of Biomedical Material Research 79B

      Pages: 284-291

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Bone regeneration by modified gene-activated matrix; Effectiveness in segmental tibial defects in rats.2006

    • Author(s)
      Endo M, Kuroda S, Kondo H, Maruoka Y, Ohya K, Kasugai S
    • Journal Title

      Journal of Tissue Engineering 12.3

      Pages: 489-497

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Biodegradable process of alpha-TCP particles and new gone formation in a rabbit cranial defect model2006

    • Author(s)
      Kihara H, Shiota M, Yamashita Y, Kasugai S
    • Journal Title

      Journal of Biomedical Material Research

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Bone regeneration by modified gene-activated matrix ; Effectiveness in segmental tibial defects in rats.2006

    • Author(s)
      Endo M, Kuroda S, Kondo H, Maruoka Y, Ohya K, Kasugai S
    • Journal Title

      Journal of Tissue Engineering

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Effectiveness of extracted-teeth as bone substitute : Application to parietal bone defects in rabbits.2005

    • Author(s)
      Tint K, Kondo H, Kuroda S, Fujimori T, Aoki K, Ohya K, Kasugai S
    • Journal Title

      Journal of Oral Tissue Engineering

      Pages: 7-16

    • NAID

      110006263673

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Local application of simvastatin to rat incisor socket : Carrier-dependent effect on bone augmentation.2005

    • Author(s)
      Sato D, Nishimura K, Ishioka T, Kondo H, Kuroda S, Kasugai S
    • Journal Title

      Journal of Oral Tissue Engineering 2(2)

      Pages: 81-85

    • NAID

      110006164164

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Molecular and cell biological properties of mouse osteogenic mesenchymal progenitor cells, Kusa.2005

    • Author(s)
      Kawashima N, Shindo K, Sakamoto K, Kondo H, Umezawa A, Kasugai S, Perbal B, Suda H, Takagi M, Katsube K
    • Journal Title

      J Bone and Mineral Metabolism

      Pages: 123-133

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Evaluation of 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer-coated dressing on surgical wounds.2005

    • Author(s)
      Katakura O, Morimoto N, Iwasaki Y, Akiyoshi K, Kasugai S
    • Journal Title

      Journal of Medical and Dental Sciences 52(2)

      Pages: 115-121

    • NAID

      110001258608

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] A new technique with calcium phosphate precipitate enhances efficiency of in vivo plasmid DNA gene transfer.2005

    • Author(s)
      Kuroda S, Kondo H, Ohya K, Kasugai S
    • Journal Title

      Journal of Pharmacological Science 97

      Pages: 227-233

    • NAID

      10025726087

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 骨造成法の現状と近未来.2005

    • Author(s)
      春日井昇平
    • Journal Title

      日本補綴学会雑誌 49(5)

      Pages: 671-675

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effectiveness of extracted-teeth as bone substitute : Application to parietal bone defects in rabbits.2005

    • Author(s)
      Tint K, Kondo H, Kuroda S, Fujimori T, Aoki K, Ohya K, Kasugai S.
    • Journal Title

      Journal of Oral Tissue Engineering 3(1)

      Pages: 7-16

    • NAID

      110006263673

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Local application of simvastatin to rat incisor socket : Carrier-dependent effect on bone augmentation.2005

    • Author(s)
      Sato D, Nishimura K, Ishioka T, Kondo H, Kuroda S, Kasugai S.
    • Journal Title

      Journal of Oral Tissue Engineering 2(2)

      Pages: 81-85

    • NAID

      110006164164

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Molecular and cell biological properties of mouse osteogenic mesenchymal progenitor cells, Kusa.2005

    • Author(s)
      Kawashima N, Shindo K, Sakamoto K, Kondo H, Umezawa A, Kasugai S, Perbal B, Suda H, Takagi M, Katsube K.
    • Journal Title

      J Bone and Mineral Metabolism 23(2)

      Pages: 123-133

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Evaluation of 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer-coated dressing on surgical wounds.2005

    • Author(s)
      Katakura O, Morimoto N, Iwasaki Y, Akiyoshi K, Kasugai S.
    • Journal Title

      Journal of Medical and Dental Sciences 52(2)

      Pages: 115-121

    • NAID

      110001258608

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A new technique with calcium phosphate precipitate enhances efficiency of in vivo plasmid DNA gene transfer.2005

    • Author(s)
      Kuroda S, Kondo H, Ohya K, Kasugai S.
    • Journal Title

      Journal of Pharmacological Science 97

      Pages: 227-233

    • NAID

      10025726087

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effectiveness of extracted-teeth as bone substitute : Application to parietal bone defects in rabbits.2005

    • Author(s)
      Tint K, Kondo H, Kuraoda S, Fujimori T, Aoki K, Ohya K, Kasugai S
    • Journal Title

      Journal of Oral Tissue Engineering 3(1)

      Pages: 7-16

    • NAID

      110006263673

    • Related Report
      2005 Annual Research Report
  • [Journal Article] New experimental model of socket healing after rat mandibular incisor extraction.2005

    • Author(s)
      SatoD, Ishioka T, Kuroda S, Kondo H, Ohya K, Kasugai S
    • Journal Title

      Journal of Clinical Periodontology (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A new technique with calcium phosphate precipitate enhances efficiency of in vivo plasmid DNA gene transfer.2005

    • Author(s)
      Kuroda S, Kondo H, Ohya K, Kasugai S
    • Journal Title

      Journal of Pharmacological Science 97(2)

      Pages: 227-233

    • NAID

      10025726087

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Osseous response to electrostatic stimulations of poled hydroxyapatite ceramics in canine diapyses.2004

    • Author(s)
      Nakamura S, Nakamura M, Kobayashi T, Sekijima Y, Kasugai S, Yamashita K
    • Journal Title

      Key Engineering Materials 254-256

      Pages: 849-852

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Histological and histomorphometrical comparative study of the degradation and osteoconductive characteristics of alpha- and beta-tricalcium phosphate (TCP) in block grafts.

    • Author(s)
      Yamada M, Shiota M, Yamashita Y, Kasugai S.
    • Journal Title

      Journal of Biomedical Material Research, 2006 Nov 14 (in press) (Epub ahead of print)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Bone increase in rat tibiae by local administration of amino-terminally truncated rhFGF-4(73-206).s

    • Author(s)
      Kuroda S, Kondo H, Ohya K, Kasugai S.
    • Journal Title

      Tissue Engineering, 2006 Dec 1 (in press) (Epub ahead of print)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 口と歯の事典(共著)2007

    • Author(s)
      春日井昇平
    • Publisher
      朝倉書店(印刷中)
    • Related Report
      2006 Annual Research Report
  • [Book] 現代歯科薬理学 第4版(小椋秀亮監修 加藤有三、篠田寿編)pp512-5152005

    • Author(s)
      春日井昇平
    • Total Pages
      548
    • Publisher
      医歯薬出版
    • Related Report
      2005 Annual Research Report
  • [Book] 現代歯科薬理学2005

    • Author(s)
      春日井昇平(共著)
    • Publisher
      医歯薬出版株式会社(印刷中)
    • Related Report
      2004 Annual Research Report

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

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