Study of embryotoxicity using the iPS/ES cells of corrosion of dental silver alloy in human saliva

• Project/Area Number: 25463040
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Prosthodontics/ Dental materials science and
• Research Institution: Osaka Dental University
• Principal Investigator: IMAI Koichi 大阪歯科大学, 歯学部, 教授 (90103100)
• Co-Investigator(Renkei-kenkyūsha): TAKEDA Shoji 大阪歯科大学, 歯学部, 名誉教授 (20067185)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 歯科用銀合金 / ES-D3細胞 / マウスiPS細胞 / 発生毒性 / 腐食 / 唾液 / 口腔 / 酸性環境 / コラーゲン

Outline of Final Research Achievements

The effects of the corrosion products of dental silver and gold- and silver-palladium alloys in the mouth on human development remain unclear. Metal ion compositions, such as silver, copper, and tin, are known to exhibit low-level embryotoxicity. The variations in embryotoxicity should be examined for the corrosion products of alloy surfaces. Using the Embryo Stem Cell Test (EST) protocol, the teratogenicity of unknown chemical substances in human fetuses can be predicted with mouse ES and 3T3 cells. In the present study, mouse iPS and ES cells were used. As a result, there was no significant difference in embryotoxicity between alloy surfaces treated or untreated with human or artificial saliva. However, mechanical scratching and subsequent immersion in hydrochloric and sulfuric acids markedly facilitated the elution of alloy elements from alloy surfaces, raising concerns about embryotoxicity.

Research Products

• [Journal Article] Study of Embryotoxicity of Commercial Dental Gold-silver-palladium Alloy by Corrosion using Acid and Artificial Saliva (2015)
  • Author(s): Imai K, Nishitani Y, Hoshika T, Akiyama M, Morita S, Iseki T, Yoshida H, Matsumoto K, Tamura I, Shida M, Sawai H, Ohkubo T, Suese K.
  • Journal Title: Journal of Oral Tissue Engineering Volume: 13 Issue: 2 Pages: 77-84
  • DOI: 10.11223/jarde.13.77
  • NAID: 130005150542
  • ISSN: 1348-9623, 1880-0823
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Influence of the ES-D3 Cell Differentiation and Cell Viability Rate by the 6 Essential Amino Acids Adding in the Minimum Essential Medium (2015)
  • Author(s): Koichi IMAI, Tatsuro MIYAKE, Isao TAMURA, Hiroki ISHIKAWA, Tomio ISEKI, Shosuke MORITA, Hirofumi SAWAI, Tadashi OHKUBO, Muneyasu SHIDA, Tetsunari NISHIKAWA, Tomoharu OKAMURA, Akio TANAKA, Kazuhiko SUESE
  • Journal Title: Journal of Oral Tissue Engineering Volume: 13 Issue: 1 Pages: 10-17
  • DOI: 10.11223/jarde.13.10
  • NAID: 130005150537
  • ISSN: 1348-9623, 1880-0823
  • Peer Reviewed / Open Access
• [Journal Article] Study of the Mutagenicity of Prototype Ag-In, Porcelain Bonding and Au-Ag-Pd Alloys Containing Indium using the Umu-test (2015)
  • Author(s): Imai K, Nishikawa T, Okamura T, Tanaka A, Miyake T, Tamura I, Ishikawa H, Iseki T, Morita S, Sawai H, Ohkubo T, Shida M, Suese K.
  • Journal Title: Journal of Oral Tissue Engineering Volume: 13 Issue: 1 Pages: 27-33
  • DOI: 10.11223/jarde.13.27
  • NAID: 130005150539
  • ISSN: 1348-9623, 1880-0823
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Preliminary Experimental Study by the Cell Differentiation and a Cell Viability on the Cell Culture Environment with the Linear Structures of Nylon Fiber Bundles (2015)
  • Author(s): Imai K, Shirai T, Ishikawa H, Honda Y, Shida M, Ogawa F, Sawai H, Ohkubo T, Miyake T, Watari F.
  • Journal Title: Nano Biomedicine Volume: 7 Issue: 1 Pages: 5-10
  • DOI: 10.11344/nano.7.5
  • NAID: 130005150625
  • ISSN: 1883-5198, 2185-4734
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Influence of MWCNTs to Myocardial Contraction Rhythms on Differentiation of ES-D3 Cells in Three-dimensional Culture (2014)
  • Author(s): Imai K, Shirai T, Watari F, Akasaka T, Nishikawa T, Okamura T, Tanaka A, Suese K, Ogawa F, Honda Y, Sawai H, Takashima H
  • Journal Title: Nano Biomedicine Volume: 6 Issue: 1 Pages: 27-34
  • DOI: 10.11344/nano.6.27
  • NAID: 130004679867
  • ISSN: 1883-5198, 2185-4734
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Study on the Possibility of Cell Growth in Tissue Culture Medium Containing Artificial Saliva (2014)
  • Author(s): Imai K, Takashima H
  • Journal Title: Journal of Oral Tissue Engineering Volume: 12 Issue: 1 Pages: 8-12
  • DOI: 10.11223/jarde.12.8
  • NAID: 130005130404
  • ISSN: 1348-9623, 1880-0823
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of the Distance from the Sample to Cell Layer in Three-dimensional Tissue Model (2014)
  • Author(s): Imai K, Takashima H
  • Journal Title: Journal of Oral Tissue Engineering Volume: 12 Issue: 1 Pages: 20-26
  • DOI: 10.11223/jarde.12.20
  • NAID: 130005130406
  • ISSN: 1348-9623, 1880-0823
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] <i>In Vitro</i> Study of Cell Differentiation by Two Type Mouse Embryo Stem Cells on the Dental Adhesives (2014)
  • Author(s): Imai K, Suese K, Honda Y, Shirai T, Ogawa F, Sawai H, Shida M, Takashima H
  • Journal Title: Journal of Oral Tissue Engineering Volume: 12 Issue: 2 Pages: 85-92
  • DOI: 10.11223/jarde.12.85
  • NAID: 130005130413
  • ISSN: 1348-9623, 1880-0823
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of C60 Fullerene on Cell Differentiation with EL-M3 and ES-R1-EGFP B2/EGFP Cell Lines (2014)
  • Author(s): Imai K, Nishikawa T, Okamura T, Tanaka A, Suese K, Honda Y, Shirai T, Ogawa F, Sawai H, Watari F
  • Journal Title: Nano Biomedicine Volume: 6 Issue: 2 Pages: 78-84
  • DOI: 10.11344/nano.6.78
  • NAID: 130005130561
  • ISSN: 1883-5198, 2185-4734
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] An attempt to study of the embryotoxicity by the diamond particles of dental diamond points with the embryonic stem cell test (2013)
  • Author(s): Imai K，Watari F，Akasaka T，Suese K，Ogawa F，Sawai H，Takashima H
  • Journal Title: Nano Biomed Volume: 5 Pages: 104-108
  • NAID: 130004679862
  • Peer Reviewed
• [Journal Article] Embryotoxic potential of the dental adhesives by the cell differentiation culture with the embryonic stem cell test (2013)
  • Author(s): Imai K，Nishikawa T，Okamura T，Tanaka A，Suese K，Honda Y，Sawai H，Takashima H
  • Journal Title: J Oral Tissue Engin Volume: 11 Pages: 148-153
  • NAID: 130004941107
  • Peer Reviewed
• [Journal Article] An attempt to in vitro embryotoxicity test using mouse ES cells and human hepatocytes (2013)
  • Author(s): Imai K，Tanoue A，Nakamura K，Honda Y，Suese K
  • Journal Title: AATEX Volume: 18 Pages: 32-37
  • NAID: 130004679893
  • Peer Reviewed
• [Journal Article] Development of sutable scaffold based on tilapia fish collagen for the long-term differentation culture of embryonic stem cells (2013)
  • Author(s): Imai K，Honda Y，Suese K
  • Journal Title: J Bio-integ Volume: 3 Pages: 75-78
  • Peer Reviewed
• [Journal Article] Development of the embryotoxicity test using the hybrid 3D cultivation technique of human hepatocytes and a mouse ES cells - use of novel feeder (2013)
  • Author(s): Imai K，Nakamura K，Tanoue A，Suese K，Honda Y，Ogawa F，Watanabe C，Ohmukai H，Takashima H
  • Journal Title: J Oral Tissue Engin Volume: 11 Pages: 51-56
  • NAID: 130004941098
  • Peer Reviewed
• [Journal Article] Embryotoxicity of the multi-walled carbon nanotubes (MWCNTs) using the three-dimensional culture of ES-D3 cells (2013)
  • Author(s): Imai K，Watari F，Suese K，Honda Y，Takashima H
  • Journal Title: Nano Biomed Volume: 5 Pages: 44-49
  • NAID: 130004679856
  • Peer Reviewed
• [Presentation] 新しいインプラントの未来永劫の発展を目指して (2016)
  • Author(s): 今井 弘一
  • Organizer: バイオインテグレーション学会第６回学術大会
  • Place of Presentation: 大阪歯科大学（大阪府大阪市中央区）
  • Year and Date: 2016-03-12
  • Invited
• [Presentation] ヒトの代謝活性因子を導入した歯科用合金組成元素の発生毒性試験法 (2015)
  • Author(s): 今井 弘一, 白井 翼, 石川 敬彬
  • Organizer: 第11回ナノ・バイオメディカル学会
  • Place of Presentation: 石巻専修大学（宮城県石巻市）
  • Year and Date: 2015-10-31
• [Presentation] 人工唾液による歯科用金銀パラジウム合金腐食生成物のin vitro発生毒性の検討 (2015)
  • Author(s): 今井 弘一, 白井 翼
  • Organizer: 第13回日本再生歯科医学会
  • Place of Presentation: 日本歯科大学新潟生命歯学部（新潟県新潟市）
  • Year and Date: 2015-08-29
• [Presentation] マウス子宮ならびに卵管由来の初代細胞をフィーダー細胞としたES細胞による発生毒性試験の試み (2014)
  • Author(s): 今井 弘一, 白井 翼, 本田 義知, 高島 宏昌
  • Organizer: 第12回日本再生歯科医学会学術大会・総会
  • Place of Presentation: 徳島大学 蔵本キャンパス 藤井節郎記念医科学センター（徳島県・徳島市）
  • Year and Date: 2014-08-26
• [Presentation] MWCNTsの３次元培養での胚性幹細胞から分化した心筋様細胞の拍動リズムの異常について (2014)
  • Author(s): 今井 弘一, 白井 翼, 本田 義知, 亘理 文夫, 高島 宏昌
  • Organizer: 第12回日本再生歯科医学会学術大会・総会
  • Place of Presentation: 徳島大学 蔵本キャンパス 藤井節郎記念医科学センター（徳島県・徳島市）
  • Year and Date: 2014-08-26
• [Presentation] In vitro embryotoxicity test using new feeder cells derived from the mouse uterus and oviduct (2014)
  • Author(s): Imai K, Honda Y, Nakamura K, Tanoue A, Takashima H
  • Organizer: 日本組織培養学会第87回大会
  • Place of Presentation: 星陵会館（東京都・千代田区）
  • Year and Date: 2014-05-30
• [Presentation] ES細胞の３次元培養によるWNCNTのin vitro発生毒性について (2014)
  • Author(s): 今井 弘一, 武田 昭二, 高島 宏昌
  • Organizer: 第８回ナノ・バイオメディカル学会大会
  • Place of Presentation: ホテルグランビア和歌山（和歌山県・和歌山市）
  • Year and Date: 2014-05-02
• [Presentation] ３次元スキャフォードを用いた金銀パラジウム合金組成元素イオンの発生毒性 (2014)
  • Author(s): 今井 弘一, 武田 昭二, 高島 宏昌
  • Organizer: 日本歯科理工学会第63回学術講演会
  • Place of Presentation: タワーホール船堀（東京都・江戸川区）
  • Year and Date: 2014-04-13
• [Presentation] マウス子宮ならびに卵管由来の初代細胞をfeeder layer とした場合におけるES細胞分化への影響 (2013)
  • Author(s): 今井 弘一, 末瀬 一彦, 本田 義知, 高島 宏昌
  • Organizer: 日本動物実験代替法学会 第26回大会
  • Place of Presentation: 京都市南区（京都テルサ）
• [Presentation] 再生医療における胚性幹細胞の有用性，応用と将来展望
  • Author(s): 今井 弘一
  • Organizer: 北海道大学大学院歯学研究セミナー，北海道歯学会例会
  • Place of Presentation: 北海道札幌市（北海道大学歯学部）
  • Invited
• [Presentation] ３次元スキャフォードを用いた金銀パラジウム合金組成元素イオンの発生毒性
  • Author(s): 今井 弘一，武田 昭二，高島 宏昌
  • Organizer: 第63回日本歯科理工学会
  • Place of Presentation: 東京都江戸川区（タワーホール船堀）