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Development of toxicity evaluation method for new dental materials using human pluripotent stem cell-derived neural crest cells

Research Project

Project/Area Number 16H05535
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Dental engineering/Regenerative dentistry
Research InstitutionNational Institutes of Biomedical Innovation, Health and Nutrition

Principal Investigator

Furue Miho  国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 ヒト幹細胞応用開発室, 招へいプロジェクトリーダー (80257310)

Co-Investigator(Kenkyū-buntansha) 二川 浩樹  広島大学, 医歯薬保健学研究科(歯), 教授 (10228140)
菅 三佳 (岸本三佳)  国立研究開発法人理化学研究所, バイオリソース研究センター, 開発研究員 (00340448)
峯 裕一  広島大学, 医歯薬保健学研究科(歯), 講師 (60605989)
福田 隆之  国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 ヒト幹細胞応用開発室, 特任研究員 (20708771)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2016: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords神経堤 / 神経堤分化 / ヒト多能性幹細胞 / 分化誘導 / in vitro 毒性評価 / 歯科材料 / 動物代替法実験 / 毒性評価 / 動物代替法 / iPS細胞 / 神経堤細胞 / 毒性予測 / 頭部神経堤 / 毒性・安全性評価 / 再生医学 / 細胞・組織 / 歯学 / 発生・分化 / 薬剤反応性
Outline of Final Research Achievements

Cleft palate is one of the most frequent congenital anomalies in the head region. At present, it is difficult to predict drug toxicity using experimental animals. We have successfully induced cranial neural crest cells from human iPS cells.  Therefore, the purpose of this study is to develop an in vitro developmental toxicity evaluation assay using human iPS cell-derived craniofacial neural crest cells with the goal of "evaluating the influence of new dental materials on the formation of the maxillofacial region". And in order to conduct the assay properly, the differentiation induction method was improved. The method was used to assess the cytotoxicity of various concentrations of three existing dental materials. The results suggest that the developed assay system can assess the toxicity of dental materials.

Academic Significance and Societal Importance of the Research Achievements

口蓋裂の病因は解明されていないが、妊娠時服用薬剤による影響もその原因のひとつであると考えられている。現状では、実験動物による評価ではヒトにおける口蓋裂発生の予測が難しい。近年、様々な歯科材料が開発されており、歯科材料が口蓋裂の原因となるようなことがあってはならない。この研究により開発したヒトiPS 細胞から頭部神経堤細胞の誘導法を用いた毒性評価アッセイにより既存の歯科材料の細胞毒性を評価することができた。新規歯科材料の毒性を評価する方法の一つとして使用されるようさらに研究を進めていきたい。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (12 results)

All 2019 2018 2017 2016

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 5 results,  Acknowledgement Compliant: 3 results) Presentation (4 results) (of which Int'l Joint Research: 1 results) Book (2 results)

  • [Journal Article] Neural Crest Cell Models of Development and Toxicity: Cytotoxicity Assay Using Human Pluripotent Stem Cell-Derived Cranial Neural Crest Cell Model2019

    • Author(s)
      Suga Mika、Furue Miho K.
    • Journal Title

      Developmental Toxicology

      Volume: 1965 Pages: 35-48

    • DOI

      10.1007/978-1-4939-9182-2_4

    • ISBN
      9781493991815, 9781493991822
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A morphology-based assay platform for neuroepithelial-like cells differentiated from human pluripotent stem cells2018

    • Author(s)
      Suga Mika、Kii Hiroaki、Ueda Naoko、Liu Yu-Jung、Nakano Takako、Dan Tomoro、Uozumi Takayuki、Kiyota Yasujiro、Furue Miho K.
    • Journal Title

      The International Journal of Developmental Biology

      Volume: 62 Issue: 9-10 Pages: 613-621

    • DOI

      10.1387/ijdb.180161mf

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Isolation and Expansion of Human Pluripotent Stem Cell-derived Hepatic Progenitor Cells by Growth Factor Defined Serum-free Culture Conditions2017

    • Author(s)
      Fukuda T., Takayama K., Hirata M., Liu Y., Yanagihara K., Suga M., Mizuguchi H., Furue M.
    • Journal Title

      Experimental Cell Research

      Volume: 352 Issue: 2 Pages: 333-345

    • DOI

      10.1016/j.yexcr.2017.02.022

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of differentiation tendency toward hepatocytes from gene expression in undifferentiated human pluripotent stem cells.2016

    • Author(s)
      Yanagihara K, Liu Y, Kanie K, Okamura M, Hirata M, Fukuda T, Suga M, Nikawa H, Kato R, Furue MK.
    • Journal Title

      Stem cells and development.

      Volume: 25(24) Issue: 24 Pages: 1884-1897

    • DOI

      10.1089/scd.2016.0099

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Biological Effects of Culture Substrates on Human Pluripotent Stem Cells.2016

    • Author(s)
      Hayashi Y, Furue MK.
    • Journal Title

      Stem Cells Int.

      Volume: Epub Issue: 1

    • DOI

      10.1155/2016/5380560

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] In Vitro Models of Cranial Neural Crest Development toward Toxicity Tests: Frog, Mouse and Human.2016

    • Author(s)
      Suga M, Hayashi Y, Furue MK.
    • Journal Title

      Oral Dis.

      Volume: - Issue: 5 Pages: 559-565

    • DOI

      10.1111/odi.12523

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] ヒト多能性幹細胞の培養における増殖因子の生理活性測定法の開発2017

    • Author(s)
      菅三佳、平井雅子、上田直子、劉有容、中野貴子、福田隆之、末盛博文、古江美保
    • Organizer
      日本組織培養学会第90 回大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒトiPS細胞由来頭部神経堤様細胞を用いたin vitro発生毒性試験法の構築に関する基礎的研究2017

    • Author(s)
      菅 三佳、三村 純代、劉 有容、中野 貴子、二川 浩樹、古江美保
    • Organizer
      日本動物実験代替法第30回大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] "The Role Of The Signaling Factors On Differentiation Of Human Embryonic Stem Cell-Derived Neural Crest Stem Cells "2016

    • Author(s)
      Suga M., Mimura S., Okada K., Kinehara M., Nikawa H., and Furue MK.
    • Organizer
      ISSCR 2016 ANNUAL MEETING
    • Place of Presentation
      SAN FRANCISCO CA USA
    • Year and Date
      2016-06-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] "Development and application of morphological evaluation for human pluripotent stem cells ヒト多能性幹細胞の形態評価測定法開発とその利用."2016

    • Author(s)
      古江-楠田美保
    • Organizer
      日本組織培養学会第 89 回大会
    • Place of Presentation
      大阪 千里ライフサイエンスセンター
    • Year and Date
      2016-05-25
    • Related Report
      2016 Annual Research Report
  • [Book] Neural crest cells models of development and toxicity Developmental Toxicology: Methods and Protocols, Second Edition, book edited by Louise Winn2018

    • Author(s)
      Suga M., Furue, KM.
    • Publisher
      Springer Science+Business Media New York
    • Related Report
      2017 Annual Research Report
  • [Book] ヒト多能性幹細胞の培養における増殖因子の生物活性の測定 (動物細胞培養における分離・精製手法と自動化技術)2018

    • Author(s)
      菅三佳、古江美保
    • Publisher
      技術情報協会
    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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