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Basic research for development of osteoregeneration therapy using mesenchymal stem cells and iPS cells

Research Project

Project/Area Number 25462900
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional basic dentistry
Research InstitutionTokyo Dental College

Principal Investigator

Azuma TOSHIFUMI  東京歯科大学, 歯学部, 教授 (00222612)

Co-Investigator(Kenkyū-buntansha) SHINO Hiromi  東京歯科大学, 歯学部, 助教 (00445446)
ONODERA Shoko  東京歯科大学, 歯学部, 助教 (90637662)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsiPS細胞 / 骨代謝 / 骨芽細胞 / 再生医療 / 疾患特異的iPS細胞 / 骨細胞 / Wnt / ヘッジホッグ / 骨再生 / 骨リモデリング / 骨欠損モデル / アルカリフォスファターゼ / 骨組織
Outline of Final Research Achievements

We developed new strategies to generate all stages of osteogenic cells including mesenchymal stem cells, pre-osteoblasts, osteoblast and osteocytes. These cells are expressed their specific marker proteins. We found that PI3K-Akt signaling is essential for early stage of osteogenesis. IGF-1, which is an effective stimulator of PI3K-Akt signaling is a potent inducer of osteogenesis. We found that IGF-1 treatment significantly improve osteogenesis. We established an effective protocol for generating osteocyte from iPS cells. We utilized this protocol to develop new strategy for osteo-regeneration therapy. We transplanted osteoblasts derived from human iPS cells to bone defects generated in Rat and found successful regeneration.We found that ALP is a specific and efficient surface marker to isolate osteolineage cells derved from iPS cells. We established effective protocol to generate osteoblast from human patient derived iPS cells.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (13 results)

All 2016 2015 2014 2013

All Journal Article (7 results) (of which Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Transplantation of human induced pluripotent stem cells carried by self-assembling peptide nanofiber hydrogel improves bone regeneration in rat calvarial bone defects.2016

    • Author(s)
      Kamichika Hayashi, Hiromi Ochiai-Shino, Takeaki Shiga, Shoko Onodera, Akiko Saito, Takahiko Shibahara Toshifumi Azuma.
    • Journal Title

      BDJ Open

      Volume: 2 Issue: 1 Pages: 15007-15007

    • DOI

      10.1038/bdjopen.2015.7

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Promoting effect of 1,25(OH)2 vitamin D3 in osteogenic differentiation from induced pluripotent stem cells to osteocyte like cells2015

    • Author(s)
      Kato H, Ochiai-Shino H, Onodera S, Saito A, Takahiko Shibahara, Azuma T
    • Journal Title

      Open Biology 5(2):140201

      Volume: 5(2) Issue: 2 Pages: 140201-140201

    • DOI

      10.1098/rsob.140201

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Additional Glucose-PTS Induction in <i>Streptococcus mutans Mutant</i> Deficient in Mannose- and Cellobiose-PTS2015

    • Author(s)
      Sato Y, Okamoto-Shibayama K, Azuma T.
    • Journal Title

      The Bulletin of Tokyo Dental College

      Volume: 56 Issue: 3 Pages: 185-18

    • DOI

      10.2209/tdcpublication.56.185

    • NAID

      130005098144

    • ISSN
      0040-8891
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glucose-PTS Involvement in Maltose Metabolism by <i>Streptococcus mutans</i>2015

    • Author(s)
      Sato Y, Okamoto-Shibayama K, Azuma T.
    • Journal Title

      The Bulletin of Tokyo Dental College

      Volume: 56 Issue: 2 Pages: 93-103

    • DOI

      10.2209/tdcpublication.56.93

    • NAID

      130005078130

    • ISSN
      0040-8891
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Akt Activation is Required for TGF-β1-Induced Osteoblast Differentiation of MC3T3-E1 Pre-Osteoblasts.2015

    • Author(s)
      Suzuki E, Ochiai-Shino H, Aoki H, Onodera S, Saito A, Saito A, Azuma T
    • Journal Title

      Plosons

      Volume: 9(12) Issue: 12 Pages: e112566-e112566

    • DOI

      10.1371/journal.pone.0112566

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel strategy for enrichment and isolation of osteoprogenitor cells from induced pluripotent stem cells based on surface marker combination.2014

    • Author(s)
      Ochiai-Shino H, Kato H, Sawada T, Onodera S, Saito A, Takato T, Shibahara T, Muramatsu T, Azuma T.
    • Journal Title

      PLOS ONE

      Volume: 9 Issue: 6 Pages: e99534-e99534

    • DOI

      10.1371/journal.pone.0099534

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppression of Lefty expression in induced pluripotent cancer cells.2013

    • Author(s)
      Saito A, Ochiai H, Okada S, Miyata N, Azuma T.
    • Journal Title

      Faseb J

      Volume: 27(6) Issue: 6 Pages: 2165-74

    • DOI

      10.1096/fj.12-221432

    • Related Report
      2013 Research-status Report
  • [Presentation] iPS細胞から骨前駆細胞分化誘導および単離の新規方法開発と骨細胞様細胞への分化誘導2014

    • Author(s)
      東俊文、齋藤暁子、小野寺晶子、加藤宏、篠宏美
    • Organizer
      第32回日本骨代謝学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-07-08 – 2014-07-10
    • Related Report
      2014 Research-status Report
  • [Presentation] PS細胞から誘導した骨芽細胞を用いた創薬評価-活性型ビタミンD3の効果判定-2014

    • Author(s)
      加藤宏、篠宏美、小野寺晶子、齋藤暁子、林宰央、長谷川大悟、柴原孝彦、東俊文
    • Organizer
      第32回日本骨代謝学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-07-08 – 2014-07-10
    • Related Report
      2014 Research-status Report
  • [Presentation] TGF-β1によるマウス前骨芽細胞の分化調節におけるPI3K/Aktシグナル伝達経路の役割2014

    • Author(s)
      鈴木瑛一、落合(篠)宏美、青木栄人、小野寺晶子、齋藤暁子、齋藤淳、東俊文
    • Organizer
      第297回東京歯科大学学会
    • Place of Presentation
      東京
    • Year and Date
      2014-06-08
    • Related Report
      2014 Research-status Report
  • [Presentation] TGF-β1 regulates osteoblast differentiation via PI3K/Akt signaling pathway2014

    • Author(s)
      Suzuki E, Ochiai-Shino H, Aoki H, Hayashi T, Takahashi J, Azuma T, Saito
    • Organizer
      TGF-β1 regulates osteoblast differentiation via PI3K/Akt signaling pathway
    • Place of Presentation
      Gifu
    • Year and Date
      2014-05-14 – 2014-05-16
    • Related Report
      2014 Research-status Report
  • [Presentation] iPS細胞から誘導した骨芽細胞を用いた創薬評価2014

    • Author(s)
      加藤宏、篠宏美、小野寺晶子、齋藤暁子、林宰央、長谷川 大悟、柴原孝彦、東俊文
    • Organizer
      第68回日本口腔科学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2014-05-07 – 2014-05-09
    • Related Report
      2014 Research-status Report
  • [Patent(Industrial Property Rights)] 骨前駆細胞2014

    • Inventor(s)
      東 俊文
    • Industrial Property Rights Holder
      東 俊文
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-03-12
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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