Induction of mandibular bone and tooth germ from embryo body formation form iPS cells in serum-, and feeder-free culture

• Project/Area Number: 26670865
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Hiroshima University
• Principal Investigator: Okamoto Tetsuji 広島大学, 医歯薬保健学研究院(歯), 教授 (00169153)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 無血清培養 / 顎骨・歯胚誘導 / iPS細胞 / センダイウイルスベクター / 無フィーダー培養 / 鎖骨頭蓋異形成症 / Noonan症候群 / 基底細胞母斑症候群 / 疾患特異的iPS細胞 / 口腔顎顔面遺伝性疾患 / 顎顔面口腔組織再生 / エンブリオボディー形成 / Noonan syndrome / ヒトiPS細胞 / 軟骨・骨形成 / 未分化性 / 多分化能 / ３胚葉分化 / 無血清培地（hESF9）

Outline of Final Research Achievements

We have successfully established and long-term cultured iPS cells from the pulp cells and peripheral blood mononuclear cells derived from Cleido cranial dysplasia, Noonan, VonRecklinghousendisease, basal nevoid cell carcinoma syndrome in serum-, feeder-,and integration-free culture. These cells exhibited several pluripotent gene expression and differentiation abilities in vitro and in vivo.The teratoma tissues derived from CCD-iPS cells and Noonan-iPA cells exhibited abnormal cartilage structures similar to the patient's cartilage. These results strongly suggest that disease-specific iPS cells might be very useful to elucidate mechanism these diseases.

Research Products

• [Journal Article] Photodynamic therapy using Photofrin and excimer dye laser treatment for superficial oral squamous cell carcinomas with long-term follow up (2016)
  • Author(s): Toratani S, Tani R, Kanda T, koizumi K, Yoshioka Y, Okamoto T
  • Journal Title: Photodiagnosis and Photodynamic Therapy Volume: 14 Pages: 104-110
  • DOI: 10.1016/j.pdpdt.2015.12.009
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Generation of cleidocranial dysplasia-specific human induced pluripotent stem cells in completely serum-, feeder-, and integration-free culture. (2015)
  • Author(s): Yamasaki S, Hamada A, Akagi E, Nakatao H, Ohtaka M, Nishimura K, Nakanishi M, Toratani S, Okamoto T.
  • Journal Title: In Vitro Cell Dev Biol Anim. Volume: 52 Issue: 2 Pages: 252-264
  • DOI: 10.1007/s11626-015-9968-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Eldecalcitol (ED-71), an Analog of 1α, 25-dihydroxyvitamin D3 as a Potential Anti-cancer Agent for Oral Squamous Cell Carcinomas. (2015)
  • Author(s): Shintani T, S.N.Z. Rosli, Takatsu F, Choon Y.F, Hayashido Y, Toratani S, Usui E, and Okamoto T
  • Journal Title: J Steroid Biochem Mol Biol Volume: 9 Pages: 79-84
  • DOI: 10.1016/j.jsbmb.2015.09.043
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comparison of the prognosis of bisphosphonate-related osteonecrosis of the jaw caused by oral and intravenous bisphosphonates. (2015)
  • Author(s): Shintani T, Hayashido Y, Mukasa H, Akagi E, Hoshino M, Ishida Y, Hamana T, Okamoto K, Kanda T, Koizumi K, Yoshioka Y, Tani R, Toratani S, Okamoto T
  • Journal Title: Int J Oral Maxillofac Surg Volume: in press Issue: 7 Pages: 125-133
  • DOI: 10.1016/j.ijom.2015.03.013
  • Peer Reviewed / Open Access
• [Journal Article] Anti-EGFR monoclonal antibody 12-93 inhibits the growth of human salivary adenocarcinoma via sub-G1 arrest and induction of apoptosis (2014)
  • Author(s): Yamamoto N, Toratani S, Okamoto T.
  • Journal Title: J Oral Maxillofac Surg, Med, Pathol Volume: 26 Issue: 2 Pages: 183-187
  • DOI: 10.1016/j.ajoms.2013.08.007
  • Peer Reviewed / Open Access
• [Journal Article] Generation of Human induced pluripotent Stem (iPS) cells in serum- and feeder-free defined culture and TGF-β1 regulation of pluripotency (2014)
  • Author(s): Yamasaki S, Taguchi Y, Shimamoto A, Mukasa H, Tahara H, Okamoto T.
  • Journal Title: PLoS One Volume: 9(1) Issue: 1 Pages: 1-13
  • DOI: 10.1371/journal.pone.0087151
  • Peer Reviewed / Open Access
• [Journal Article] 1α,25(OH)2D3 inhibits FGF-2 release from oral squamous cell carcinoma cells through downregulation of HBp17/FGFBP-1 (2014)
  • Author(s): S. N. Zawani B. Rosli, Shintani T. Hayashido Y, Toratani S, Okamoto T.
  • Journal Title: In Vitro Cell. Devel. Biol.-Anim Volume: Oct;50(9) Issue: 9 Pages: 802-806
  • DOI: 10.1007/s11626-014-9787-5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Overexpression of integrin αv facilitates proliferation and invasion of oral squamous cell carcinoma cells via MEK/ERK signaling pathway that is activated by interaction of integrin αvβ8 with type Ⅰ collagen (2014)
  • Author(s): Hayashido Y, Kitano H, Sakaue T, Fujii T, Suematsu M, Sakurai S, Okamoto T
  • Journal Title: Int J Oncol Volume: 45(5) Issue: 5 Pages: 1875-1882
  • DOI: 10.3892/ijo.2014.2642
  • Peer Reviewed / Open Access
• [Presentation] インテグレーションフリー・フィーダーフリー・無血清培養系での疾患特異的iPS細胞の樹立 (2015)
  • Author(s): 濱田充子、中峠洋隆、大林史誠、安井多恵子、赤木恵理、山崎佐知子、大高真奈美、中西真人、虎谷茂昭、岡本哲治
  • Organizer: 第52回日本口腔組織培養学会
  • Place of Presentation: 徳島
  • Year and Date: 2015-11-21
• [Presentation] フィーダー細胞フリー・無血清培養系での ヒト人工多能性幹細胞(hiPSC)の 誘導と長期培養 ―宿主細胞およびウイルスベクターの比較― (2015)
  • Author(s): 赤木恵理、山崎佐知子、濱田充子、中峠洋隆、大林史誠、安井多恵子、田口有紀、大高真奈美、西村健、中西真人、谷亮治、虎谷茂昭、岡本哲治
  • Organizer: 第52回日本口腔組織培養学会11月21日
  • Place of Presentation: 徳島
  • Year and Date: 2015-11-21
• [Presentation] Generation and maintenance of integration-free human induced pluripotent stem (hiPS) cells from peripheral blood mononuclear cells in serum- and feeder-free growth factor defined medium (2015)
  • Author(s): 中峠洋隆山崎佐知子赤木恵理濱田充子大高真奈美西村健中西真人岡本哲治
  • Organizer: The Society for In Vitro Biology
  • Place of Presentation: Tucson, Arizona, USA
  • Year and Date: 2015-05-30
  • Int'l Joint Research
• [Presentation] センダイウイルスを用いたフィーダー細胞フリー・完全無血清培養系でのヒト単核球からのヒトiPS細胞の樹立と維持に関する研究 (2015)
  • Author(s): 赤木恵理、山崎佐知子、濱田充子、中峠洋隆、大高真奈美、西村健、中西真人、虎谷茂昭、岡本哲治
  • Organizer: 第69回NPO法人日本口腔科学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-05-13
• [Presentation] Reprogramming efficiencies of hiPS cells with various virus vectors in serum- and feeder-free culture conditions. (2014)
  • Author(s): Eri AKAGI, Sachiko YAMASAKI, Atsuko HAMADA, Yuki TAGUCHI, Hanae MUKASA, Manami OHTAKA, Ken NISHIMURA, Mahito NAKANISHI, and Tetsuji OKAMOTO
  • Organizer: World Congress of Society for In Vitro Biology,
  • Place of Presentation: Hyatt Regency Savannah, Savannah, Georgia, USA
  • Year and Date: 2014-05-30 – 2014-06-04
• [Presentation] Generation and maintenance of human induced pluripotent stem cells in serum- and feeder-free culture using Sendai virus vectors. (2014)
  • Author(s): HAMADA, Sachiko YAMASAKI, Eri AKAGI, Manami OHTAKA, Ken NISHIMURA, Mahito NAKANISHI, Tetsuji OKAMOTO
  • Organizer: World Congress of Society for In Vitro Biology,
  • Place of Presentation: Hyatt Regency Savannah, Savannah, Georgia, USA
  • Year and Date: 2014-05-30 – 2014-06-04
• [Presentation] センダイウイルスを用いたフィーダー細胞フリー・完全無血清培養系での末梢リンパ球からのhiPS細胞の樹立と維持に関する研究、 (2014)
  • Author(s): 赤木恵理, 山崎佐知子, 他
  • Organizer: 日本口腔科学会学術集会
  • Place of Presentation: 京王プラザ、東京
  • Year and Date: 2014-05-07 – 2014-05-09
• [Presentation] 扁平上皮癌細胞でのオートファジーによる インテグリンαvのプロセシング、 (2014)
  • Author(s): 末松 美玲, 林堂安貴,他:
  • Organizer: 日本口腔科学会学術集会
  • Place of Presentation: 京王プラザ、東京
  • Year and Date: 2014-05-07 – 2014-05-09
• [Presentation] センダイウイルスを用いたフィーダーフリー・ 無血清培養系での歯髄細胞由来hiPS細胞の樹立と長期培養、 (2014)
  • Author(s): 濱田充子, 山崎佐知子,他：
  • Organizer: 日本口腔科学会学術集会
  • Place of Presentation: 京王プラザ、東京
  • Year and Date: 2014-05-07 – 2014-05-09