Study of the cancer stem cell induction from the human iPS cell

• Project/Area Number: 26670862
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Gifu University
• Principal Investigator: SHIBATA TOSHIYUKI 岐阜大学, 医学(系)研究科(研究院), 教授 (50226172)
• Co-Investigator(Kenkyū-buntansha): KAWAGUCHI Tomoko 岐阜大学, 医学部附属病院, 医員 (30509815) ; IIDA Kazuki 岐阜大学, 医学部附属病院医員, 助教 (30585237) ; TAMAOKI Naritaka 岐阜大学, 大学院医学系研究科, 助教 (40585303)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: iPS細胞 / ヒト歯髄細胞 / がん化

Outline of Final Research Achievements

One of final purpose of this study is to establish the safety procedure of iPS cells avoiding the carcinogenesis. Our new knowledges from this study are as follows; In the high efficiency of iPS cells and the induction of high quality iPS cells from Dental Pulu Stem Cells (DPSC), enhancement of epithelial marker (E-cadherin), that is epithelial and mesenchymal translation, and enhancement of DLX4 expression (DLX4 is engaged in the TGF-β signal translation) play an important roles in the iPS cell induction efficiency avoiding malignant progression. Furthermore, we carried out the iPS cell induction under TGF-β stimulation. TGF-β stimulation significantly reduced the efficiency of iPS cell induction without the alternation of smad signals. During the analysis of cancer cell effects on the iPS cells, culture conditioned medium possibly affect the iPS cell nature itself including differentiation ability.

Research Products

• [Journal Article] Transforming growth factor-β1 induces invasion ability of HSC-4 human oral squamous cell carcinoma cells through the Slug/Wnt-5b/MMP-10 signalling axis. (2016)
  • Author(s): Hino M, Kamo M, Saito D, Kyakumoto S, Shibata T, Mizuki H, Ishisaki A.
  • Journal Title: Journal of Biochemistry Volume: March 2 Issue: 6 Pages: 1-10
  • DOI: 10.1093/jb/mvw007
  • NAID: 40020869454
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Conditioned medium of dental pulp cells stimulated by Chinese propolis show neuroprotection and neurite extension in vitro (2015)
  • Author(s): Kudo D, Inden M, Sekine S, Tamaoki N, Iida K, Naito E, Watanabe K, Kamishina H, Shibata T, Hozumi I.
  • Journal Title: Neurosci Lett Volume: 589 Pages: 92-97
  • DOI: 10.1016/j.neulet.2015.01.035
  • Peer Reviewed / Open Access
• [Journal Article] The homeobox gene DLX4 promotes generation of human induced pluripotent stem cells (2014)
  • Author(s): Naritaka Tamaoki, Kazutoshi Takahashi, Hitomi Aoki, Kazuki Iida, Tomoko Kawaguchi, Daijirou Hatakeyama, Masatoshi Inden, Naoyuki Chosa, Akira Ishisaki, Takahiro Kunisada, Toshiyuki Shibata, Naoki Goshima, Shinya Yamanaka, and Ken-ichi Tezuka
  • Journal Title: Scientific Reports Volume: なし Issue: 1 Pages: 7283-7283
  • DOI: 10.1038/srep07283
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Derivation of iPSCs after culture of human dental pulp cells under defined conditions (2014)
  • Author(s): Takeda-Kawaguchi T, Sugiyama K, Chikusa S, Iida K, Aoki H, Tamaoki N, Hatakeyama D, Kunisada T, Shibata T, Fusaki N, Tezuka K.
  • Journal Title: PLoS One. 2014 Dec 18;9(12):e115392 Volume: 18 Issue: 12 Pages: 1-15
  • DOI: 10.1371/journal.pone.0115392
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] The homeobox gene DLX4 promotes generation of human induced pluripotent srem cells (2014)
  • Author(s): T.Tamaoki, K Takahashi, H Aoki, K Iida, T Kawaguchi, D Hatakeyama, M Indan, N Chousa, A Isisaki, T Kunisada, T Shibata, N Gotou, S Yamanaka, K Tezuka
  • Organizer: ASBMR（アメリカ骨代謝学会）
  • Place of Presentation: テキサス州ヒューストン（米国）
  • Year and Date: 2014-09-12 – 2014-09-16
• [Patent(Industrial Property Rights)] Method for producing induced pluripotent stem cells (2016)
  • Inventor(s): SHIBATA Toshiyuki
  • Industrial Property Rights Holder: SHIBATA Toshiyuki
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-01-16
  • Overseas