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抜去歯由来幹細胞による骨、歯髄、象牙質再生療法と発展的細胞治療法、同種移植研究

Research Project

Project/Area Number 20659297
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Conservative dentistry
Research InstitutionNagoya University

Principal Investigator

山田 陽一  名古屋大学, 医学部附属病院, 助教 (20345903)

Co-Investigator(Kenkyū-buntansha) 上田 実  名古屋大学, 医学系研究科, 教授 (00151803)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2010: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2009: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2008: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywords再生医療 / 幹細胞 / 細胞治療法 / 同種移植 / 歯内療法 / 骨再生
Research Abstract

昨年度に引き続き、骨髄間葉系幹細胞(BMMSCs)に代わる幹細胞源として期待されている乳歯および永久歯歯髄幹細胞を用いた細胞治療法の開発について、特に歯槽骨再生および同種移植に焦点をあて、さらなる研究を行った。生後2ヶ月の子イヌより抜去した乳歯および親イヌより抜去した永久歯から歯髄由来細胞を単離、培養した後、親イヌ顎骨に直径10mmの歯槽骨欠損モデルを作成し、得られた乳歯歯髄由来細胞、永久歯歯髄由来細胞およびBMMSCsを骨芽細胞分化誘導培地にて培養後、それぞれ移植した。生理活性物質および足場としては、多血小板血漿(PRP)を用いた。その結果、移植後4、8週において、コントロール群(欠損のみ、PRPのみ)では骨形成がほとんど得られなかったのに対し、乳歯歯髄由来細胞、永久歯歯髄由来細胞およびBMMSCs移植群においては良好な骨形成が確認された。再生骨について免疫組織学的評価を行ったところ、Osteocalcin陽性を示した。また、移植後8週における骨占有率は、細胞移植群がコントロール群に対して有意に高い値を示したが、細胞間での有意差は認められなかった。その後細胞移植8週後に細胞移植部へのインプラント埋入行い、16週後に屠殺し、組織学的、組織形態学的評価を行ったところ、インプラントと再生骨の骨結合率bone-implant contact (BIC)は、コントロール群と比較し細胞移植群では有意に高いことが示された。細胞移植により再生された骨と埋入されたインプラントとの骨結合率が良好であったことから、骨欠損部への歯髄由来細胞移植が咬合機能回復に有用である可能性が示唆された。さらに、乳歯歯髄由来細胞を用いた世代間を超えた移植により良好な骨再生が得られたことから、同種移植の可能性が示唆された。なお、この成果はCell Transplant (2010 Epub)において発表した。

Report

(3 results)
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (63 results)

All 2011 2010 2009 2008

All Journal Article (30 results) (of which Peer Reviewed: 17 results) Presentation (29 results) Book (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Human Deciduous Teeth Dental Pulp Cells (hDPC) with Basic Fibroblast Growth Factor (b-FGF) Enhance Wound Healing of Skin Defect2011

    • Author(s)
      Nishino, Y
    • Journal Title

      J Craniofac surg

      Volume: In press

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stem cells from human exfoliated deciduous teeth( SHED) enhance wound healing and possibility of novel cell therapy.2011

    • Author(s)
      Nishino, Y
    • Journal Title

      Cytotherapy

      Volume: In press

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of the Wnt signaling patkways during cell culture of human mesenchymal stem cells for efficient bone regeneration.2011

    • Author(s)
      Katagiri, W
    • Journal Title

      Orai science Int

      Volume: In press

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Periodontal perspectives from Asia : Current and future periodontal tissue engineering.2011

    • Author(s)
      Izumi, Y
    • Journal Title

      Periodontol 2000

      Volume: In press

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Promising cell-based therapy for bone regeneration using stem cells from deciduous teeth, dental pulp, and bone marrow.2010

    • Author(s)
      Yamada, Y
    • Journal Title

      Cell Transplant

      Volume: Epub ahead of print

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 近未来の歯科医療を考える再生医療とインプラント2010

    • Author(s)
      山田陽一
    • Journal Title

      岐歯新報

      Volume: 771 Pages: 44-49

    • Related Report
      2010 Annual Research Report
  • [Journal Article] A feasibility of useful cell-based therapy by bone regeneration with deciduous tooth stem cells, dental pulp stem cells, or bone marrow-derived mesenchymal stem cells for clinical study using tissue engineering technology.2010

    • Author(s)
      Yamada, Y
    • Journal Title

      Tissue Eng Part A. (Epub ahead of print)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone regeneration with self-assembling peptide nanofiber scaffolds in tissue engineering for osseointegration of dental implants.2010

    • Author(s)
      Kohgo, T
    • Journal Title

      Int J Periodont Rest (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 下顎無歯顎高度歯槽骨萎縮症例にインプラントを用いて咬合改善を行った1症例2010

    • Author(s)
      山田陽一
    • Journal Title

      日本口腔インプラント学会誌 (In press)

    • NAID

      10027087774

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 骨延長法により2次修正をした血管柄付き肩甲骨による下顎再建の1例2010

    • Author(s)
      日比英晴
    • Journal Title

      日本口腔外科学会誌 56

      Pages: 23-27

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article]2010

    • Author(s)
      山田陽一
    • Journal Title

      実験医学 再生医療の最前線2010 第3章 幹細胞の分化誘導と臨床応用 歯髄幹細胞の再生医療における可能性(羊土社)

      Pages: 127-133

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Stem Cell Proliferation Pathways Comparison Between Human Exfoliated Deciduous Teeth and Dental Pulp Stem Cells by Gene Expression Profile From Promising Dental Pulp2009

    • Author(s)
      Nakamura, S
    • Journal Title

      J Endod 35(11)

      Pages: 1536-1542

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Self-assembling peptide nanofiber scaffolds, platelet rich plasma, and mesenchymal stem cells for injectable bone regeneration with tissue engin eerine.2009

    • Author(s)
      Yoshimi, R
    • Journal Title

      J Craniofac Surg 20(5)

      Pages: 1523-1530

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Injectable soft-tissue augmentation by tissue engineering and regenerative medicine with human mesenchymal stem cells, platelet-rich plasma, and hyaluronic acid scaffolds.2009

    • Author(s)
      Okabe, K
    • Journal Title

      Cytotherapy 11(3)

      Pages: 307-316

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 総説 : 体性幹細胞を用いた顎顔面骨の再生医療2009

    • Author(s)
      山田陽一
    • Journal Title

      日本口腔外科学会雑誌 55

      Pages: 2-14

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 歯髄幹細胞による骨再生と臨床応用の可能性2009

    • Author(s)
      山田陽一
    • Journal Title

      医学のあゆみ 231

      Pages: 8798-8802

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 体性幹細胞による臨床応用とその展望2009

    • Author(s)
      山田陽一
    • Journal Title

      腎と透析 66

      Pages: 3297-3305

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 乳歯幹細胞研究バンク2009

    • Author(s)
      中村さやか
    • Journal Title

      総合臨床 58

      Pages: 33-35

    • Related Report
      2009 Annual Research Report
  • [Journal Article]2009

    • Author(s)
      山田陽一
    • Journal Title

      季刊 歯科医療 歯周組織再生医療の分類、基礎と臨床 5)細胞移植(第一歯科出版)

      Pages: 29-37

    • Related Report
      2009 Annual Research Report
  • [Journal Article]2009

    • Author(s)
      山田陽一
    • Journal Title

      口腔と全身疾患, 第7編 歯科医学と生命の結びつき 3)歯科医療の再生(iPS、GTR、エムドゲイン、インプラント、全身疾患への応用)(クインテッセンス出版)

      Pages: 188-192

    • Related Report
      2009 Annual Research Report
  • [Journal Article]2009

    • Author(s)
      山田腸一
    • Journal Title

      幹細胞の分化誘導と応用 第2編 幹細胞の特性と制御機構および作製技術 4章 体性幹細胞 1)歯髄幹細胞(エヌ・ティー・エス)

      Pages: 45-54

    • Related Report
      2009 Annual Research Report
  • [Journal Article]2009

    • Author(s)
      山田陽一
    • Journal Title

      幹細胞の分化誘導と応用 第4編 幹細胞の分化誘導と移植技術 3章 再生医療技術 6)乳歯幹細胞を利用した歯の再生医療技術(エヌ・ティー・エス)

      Pages: 268-275

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Injectable Tissue-Engineered Bone using Autogenous Bone Marrow derived Stromal Cells for Maxillary Sinus Augmentation : Clinical Application Report - From 2 to 6 Years Follow Up-2008

    • Author(s)
      Yamada, Y., et al
    • Journal Title

      Tissue Eng 14

      Pages: 1699-1707

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Culture medium study of human mesenchymal stem cells for practical use of tissue engineering and regenerative medicine2008

    • Author(s)
      Nakamura, S., et al
    • Journal Title

      Biomed Mater Eng 18

      Pages: 129-136

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 多発性骨髄腫に対するビスフォスフォネート投与に関連したと考えられる上顎骨壊死の1例2008

    • Author(s)
      片桐渉, ら
    • Journal Title

      日本口腔外科学会誌 54

      Pages: 256-260

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Injectable bone applied for ridge augmentation and dental implant placement : human progress study2008

    • Author(s)
      Ueda, M., et al
    • Journal Title

      Implant Dent 17

      Pages: 82-90

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Promoted New Bone Formation in Maxillary Distraction Osteogenesis Using a Tissue-engineered Osteogenic Material2008

    • Author(s)
      Kinoshita, K., et al
    • Journal Title

      J. Craniofac. surg 19

      Pages: 80-87

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 老化による歯槽骨の吸収とアンチエイジング再生医療2008

    • Author(s)
      山田陽一, ら
    • Journal Title

      医学のあゆみ 224

      Pages: 545-549

    • Related Report
      2008 Annual Research Report
  • [Journal Article] 「乳歯幹細胞研究バンク」設立について2008

    • Author(s)
      山田陽一, ら
    • Journal Title

      日本歯科評論 68

      Pages: 170-172

    • NAID

      40015877508

    • Related Report
      2008 Annual Research Report
  • [Journal Article] 乳歯幹細胞研究バンク2008

    • Author(s)
      中村さやか, ら
    • Journal Title

      総合臨床 58

      Pages: 33-35

    • Related Report
      2008 Annual Research Report
  • [Presentation] A novel clinical innovation for periodontal disease and dental implant treatment by tissue engineering and regenerative medicine (TERM) using stem cell technolog y.2010

    • Author(s)
      Yamada, Y
    • Organizer
      The 96th Annual Meeting of the American Academy of Periodontology
    • Place of Presentation
      Waikiki, USA
    • Year and Date
      2010-11-01
    • Related Report
      2010 Annual Research Report
  • [Presentation] 遺伝子プロファイリングによる骨髄幹細胞と歯髄幹細胞のキャラクタライズスタディー2010

    • Author(s)
      原憲史
    • Organizer
      第55回日本口腔外科学会総会
    • Place of Presentation
      千葉
    • Year and Date
      2010-10-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Cell-based therapy with dental pulp stem cells for bone regeneration.2010

    • Author(s)
      Yamada, Y
    • Organizer
      International Association for Dental Research
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2010-07-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Proliferation of SHED and relation to Wnt signaling pathway.2010

    • Author(s)
      Katagiri, W
    • Organizer
      International Association for Dental Research
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2010-07-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Optimized study for dental pulp stem Cell-based therapy by ready-to-use.2010

    • Author(s)
      Umemura, E
    • Organizer
      International Association for Dental Research
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2010-07-16
    • Related Report
      2010 Annual Research Report
  • [Presentation] Characterization of dental pulp stem cells for mineralized tissue regeneration.2010

    • Author(s)
      Nakamura, S
    • Organizer
      International Association for Dental Research
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2010-07-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] Transplantation of dental pulp stem cells in spiral cord injury.2010

    • Author(s)
      Sakai, K
    • Organizer
      International Association for Dental Research
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2010-07-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] 乳歯および永久歯歯髄細胞による骨再生・インプラント治療への応用2010

    • Author(s)
      中村さやか
    • Organizer
      第132回日本歯科保存学会春季学術大会
    • Place of Presentation
      熊本
    • Year and Date
      2010-06-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] 最新の歯周治療の革新-そのコンセプト・技術・器材- 組織幹細胞を用いた歯周組織再生治療のパラダイムシフト2010

    • Author(s)
      山田陽一
    • Organizer
      第53回日本歯周病学会春季学術大会
    • Place of Presentation
      盛岡
    • Year and Date
      2010-05-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] Cell based therapy on bone regeneration with deciduous tooth stem cells, dentalpulp stem cells, or bone marrow-derived mesenchymal stem cells for clinical study by tissue engineering and regenerative medicine.2010

    • Author(s)
      Yamada, Y
    • Organizer
      The third pan pacific symposium on stem cells research
    • Place of Presentation
      Taiwan
    • Year and Date
      2010-04-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] Recent advances of tissue engineering in dentistry2009

    • Author(s)
      Yamada, Y
    • Organizer
      17th general assembly, the 32th annual scientific meeting, and dental exhibition of the association for dental sciences of the republic of china
    • Place of Presentation
      Kaohsiung, Taiwan
    • Year and Date
      2009-11-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] Clinical and basic research in tissue-engineered bone regeneration bone regeneration for general implant.2009

    • Author(s)
      Yamada, Y
    • Organizer
      2009 annual congress of the academy of oral implantology
    • Place of Presentation
      Taipei, Taiwan
    • Year and Date
      2009-10-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] 乳歯・永久歯由来歯髄幹細胞による顎顔面領域再生への可能性2009

    • Author(s)
      山田陽一
    • Organizer
      第54回日本口腔外科学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2009-10-10
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒト乳歯歯髄由来幹細胞の細胞特性の検討 : 増殖能とWnt/βカテニン経路の関連2009

    • Author(s)
      片桐渉
    • Organizer
      第54回日本口腔外科学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2009-10-10
    • Related Report
      2009 Annual Research Report
  • [Presentation] 乳歯歯髄幹細胞による皮膚創傷治癒効果の検討2009

    • Author(s)
      西野雄大
    • Organizer
      第54回日本口腔外科学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2009-10-10
    • Related Report
      2009 Annual Research Report
  • [Presentation] 幹細胞を用いた再生医療による新規歯周病治療法のパラダイムシフト-臨床経過から-2009

    • Author(s)
      山田陽一
    • Organizer
      第52回日本歯周病学会春季学術大会
    • Place of Presentation
      岡山
    • Year and Date
      2009-05-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] Update of oral and maxillofacial regenerative medicine using stem cell technology.2009

    • Author(s)
      Yamada, Y
    • Organizer
      The 50th anniversary congress of the Korean association of oral and maxillofacial surgeons
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2009-04-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] Clinical application using injectable tissueengineered bone for minimally invasive and aesthetic dental implant treatment2009

    • Author(s)
      Yamada, Y
    • Organizer
      18th Annual Scientific Meeting of European Association for Osseointegration
    • Place of Presentation
      Monaco
    • Related Report
      2009 Annual Research Report
  • [Presentation] Characterization and possibility of bone regeneration for dental implant using dental pulp stem cells(DPSCs)and stem cells from human exfoliated deciduous teeth(SHED)as novel stem cell origin2009

    • Author(s)
      Nakamura, S
    • Organizer
      18th Annual Scientific Meeting of European Association for Osseointegration
    • Place of Presentation
      Monaco
    • Related Report
      2009 Annual Research Report
  • [Presentation] 歯髄幹細胞による再生医療を用いたインプラント治療への応用 -乳歯、永久歯歯髄幹細胞による骨再生パラダイムシフトー2009

    • Author(s)
      山田陽一
    • Organizer
      第39回日本口腔インプラント学会総会
    • Place of Presentation
      大阪
    • Related Report
      2009 Annual Research Report
  • [Presentation] 歯髄幹細胞による創傷治癒、骨再生医療への展開-乳歯・永久歯歯髄幹細胞の比較2009

    • Author(s)
      山田陽一
    • Organizer
      第130回日本歯科保存学会学術大会
    • Place of Presentation
      札幌
    • Related Report
      2009 Annual Research Report
  • [Presentation] 乳歯および永久歯歯髄細胞の遺伝子発現プロファイルの比較検討2009

    • Author(s)
      中村さやか
    • Organizer
      第130回日本歯科保存学会学術大会
    • Place of Presentation
      札幌
    • Related Report
      2009 Annual Research Report
  • [Presentation] ヒト乳歯歯髄由来幹細胞の特性の検討2008

    • Author(s)
      中村さやか, ら
    • Organizer
      第129回日本歯科保存学会秋季学術大会
    • Place of Presentation
      富山
    • Year and Date
      2008-11-06
    • Related Report
      2008 Annual Research Report
  • [Presentation] 乳歯由来歯髄幹細胞は血管新生・神経再生を促進する2008

    • Author(s)
      庵原耕一郎, ら
    • Organizer
      第129回日本歯科保存学会秋季学術大会
    • Place of Presentation
      富山
    • Year and Date
      2008-11-06
    • Related Report
      2008 Annual Research Report
  • [Presentation] 同一患者より得た埋伏歯および乳歯歯髄由来幹細胞の細胞特性の比較2008

    • Author(s)
      片桐渉, ら
    • Organizer
      第62回日本口腔科学会総会
    • Place of Presentation
      徳島
    • Year and Date
      2008-10-21
    • Related Report
      2008 Annual Research Report
  • [Presentation] 口腔外科領域における再生医療、その後の進歩;体性幹細胞を用いた顎顔面骨の再生医療2008

    • Author(s)
      山田陽一, ら
    • Organizer
      第53回日本口腔外科学会
    • Place of Presentation
      徳島
    • Year and Date
      2008-10-20
    • Related Report
      2008 Annual Research Report
  • [Presentation] 顎顔面再生医療の美容への応用2008

    • Author(s)
      山田陽一, ら
    • Organizer
      第94回日本美容外科学会
    • Place of Presentation
      東京
    • Year and Date
      2008-05-11
    • Related Report
      2008 Annual Research Report
  • [Presentation] A novel sinus augmentation using tissue-engineered bone for immediate function2008

    • Author(s)
      Sayaka Nakamura, et al.
    • Organizer
      17^<th> annual scientific meeting of European association for osseointegration
    • Place of Presentation
      Warsaw, Poland
    • Related Report
      2008 Annual Research Report
  • [Presentation] 歯槽骨再生医療のインプラント治療への臨床応用とその経過2008

    • Author(s)
      山田陽一, ら
    • Organizer
      第38回日本口腔インプラント学会総会
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report
  • [Book] 実験医学再生医療の最前線2010第3章幹細胞の分化誘導と臨床応用歯髄幹細胞の再生医療における可能性2010

    • Author(s)
      山田陽一
    • Publisher
      羊土社
    • Related Report
      2010 Annual Research Report
  • [Book] Alveolar distraction osteogenesis and tissue engineering2008

    • Author(s)
      Jensen, OT., et al.
    • Publisher
      Quintessence Publishing
    • Related Report
      2008 Annual Research Report
  • [Book] 進み続ける細胞移植治療の実際-再生医療の実現に向けた科学・技術と周辺要素の理解-2008

    • Author(s)
      山田陽一, ら
    • Publisher
      メディカルドウ(株)
    • Related Report
      2008 Annual Research Report
  • [Patent(Industrial Property Rights)] 乳歯歯髄幹細胞に特徴的な遺伝子発現群の利用2009

    • Inventor(s)
      山田陽一、中村さやか、上田実
    • Industrial Property Rights Holder
      名古屋大学
    • Industrial Property Number
      2009-122379
    • Filing Date
      2009-05-20
    • Related Report
      2009 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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