Modeling the development of notochord and floor plate with human induced pluripotent stem cells.

• Project/Area Number: 24592124
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Kyoto University
• Principal Investigator: MORIZANE Asuka 京都大学, iPS細胞研究所, 助教 (10528730)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 多能性幹細胞 / 脊索 / 神経 / 分化誘導

Outline of Final Research Achievements

Notochord appears in the developing embryo close to the neural tube. It secretes Sonic hedgehog (Shh) and Noggin that induce specific of neurons such as dopaminergic neurons.The research of notochord has been proceeded with Xenopus or Chick. Regarding human, as it is difficult to use its embryo, the notochord of human development has not been studied. In this study, human pluripotent stem cells made it possible to generate the in vitro model of development of human notochord and neural tube. Many combinations of known factors and small molecules has been tried to induce human notochord from pluripotent stem cells. Finally the markers expressed in notochord such as Shh and Foxa2 were observed in the induced cells. This invented protocol enables the study of notochord development with human cells that has been difficult without pluripotent stem cells.

Research Products

• [Journal Article] Parkinson病に対する神経細胞移植 (2014)
  • Author(s): 森実飛鳥、高橋 淳
  • Journal Title: 診断と治療 Volume: 102 Pages: 1549-54
• [Journal Article] パーキンソン病の新しい治療ー再生医療を中心に (2014)
  • Author(s): 森実飛鳥、高橋 淳
  • Journal Title: 老年精神医学雑誌 Volume: 25 Pages: 1234-40
• [Journal Article] A novel efficient feeder-free culture system for the derivation of human induced pluripotent stem cells. (2014)
  • Author(s): Nakagawa M, Taniguchi Y, Senda S, Takizawa N, Ichisaka T, Asano K, Morizane A, Doi D, Takahashi J, Nishizawa M, Yoshida Y, Toyoda T, Osafune K, Sekiguchi K, YamanakaS.
  • Journal Title: Scientific Reports Volume: 4 Issue: 1 Pages: 3594-3594
  • DOI: 10.1038/srep03594
  • NAID: 120005357344
  • Peer Reviewed
• [Journal Article] Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation (2014)
  • Author(s): Daisuke Doi, Bumpei Samata, Mitsuko Katsukawa, Tetsuhiro Kikuchi, Asuka Morizane, Yuichi Ono, Kiyotoshi Sekiguchi, Masato Nakagawa, Malin Parmar, Jun Takahashi
  • Journal Title: Stem Cell Reports Volume: 2 Issue: 3 Pages: 337-350
  • DOI: 10.1016/j.stemcr.2014.01.013
  • Peer Reviewed / Open Access
• [Journal Article] Neural induction with a dopaminergic phenotype from human pluripotent stem cells through a feeder-free floating aggregation culture. (2013)
  • Author(s): Morizane A, Doi D, Takahashi J
  • Journal Title: Methods Mol BioL Volume: 1018 Pages: 11-19
  • DOI: 10.1007/978-1-62703-444-9_2
  • ISBN: 9781627034432, 9781627034449
• [Journal Article] Differentiation-defective phenotypes revealed by large-scale analyses of human pluripotent stem cells. (2013)
  • Author(s): Michiyo Koyanagi-Aoi, Mari Ohnuki, Kazutoshi Takahashi, Keisuke Okita, Hisashi Noma, Yuka Sawamura, Ito Teramoto, Megumi Narita, Yoshiko Sato, Tomoko Ichisaka, Naoki Amano, Akira Watanabe, Asuka Morizane, Yasuhiro Yamada, Tosiya Sato, Jun Takahashi and Shinya Yamanaka
  • Journal Title: Proc Natl Acad Sci U S A Volume: 110 Issue: 51 Pages: 20569-74
  • DOI: 10.1073/pnas.1319061110
  • NAID: 120005348335
  • Peer Reviewed
• [Journal Article] Direct Comparison of Autologous and Allogeneic Transplantation of iPSC Derived Neural Cells in the Brain of a Nonhuman Primate Stem (2013)
  • Author(s): Morizane A, Doi D, Kikuchi T, Okita K, Hotta A, Kawasaki T, Hayashi T, Onoe H, Shiina T, Yamanaka S, Takahashi J.
  • Journal Title: Stem Cell Reports Volume: 1 Issue: 4 Pages: 1-10
  • DOI: 10.1016/j.stemcr.2013.08.007
  • Peer Reviewed
• [Journal Article] γ-Secretase Inhibitors Prevent Overgrowth of Transplanted Neural Progenitors Derived from Human-Induced Pluripotent Stem Cells. (2013)
  • Author(s): Ogura A, Morizane A, Nakajima Y, et al.
  • Journal Title: Stem Cells Dev Volume: 22 Issue: 3 Pages: 374-382
  • DOI: 10.1089/scd.2012.0198
• [Journal Article] Prolonged maturation culture favors a reduction in the tumorigenicity and the dopaminergic function of human ESC-derived neural cells in a primate model of Parkinson's disease (2012)
  • Author(s): Doi D, Morizane A, Kikuchi T, Onoe H, Hayashi T, Kawasaki T, Motono M, Sasai Y, Saiki H, Gomi M, Yoshikawa T, Hayashi H, Shinoyama M, Refaat MM, Suemori H, Miyamoto S, Takahashi J.
  • Journal Title: Stem Cells Volume: 30(5) Issue: 5 Pages: 935-45
  • DOI: 10.1002/stem.1060
  • Peer Reviewed
• [Journal Article] Functional recovery of the murine brain ischemia model using human induced pluripotent stem cell-derived telencephalic progenitors. (2012)
  • Author(s): Gomi M, Takagi Y, Morizane A., et al.
  • Journal Title: Brain Res Volume: 1459 Pages: 52-60
  • DOI: 10.1016/j.brainres.2012.03.049
  • Peer Reviewed
• [Journal Article] Drug screening for ALS using patient-specific induced pluripotent stem cells (2012)
  • Author(s): Egawa, N., Kitaoka, S., Tsukita, K., Naitoh, M., Takahashi, K., Yamamoto, T., Adachi, F., Kondo, T., Okita, K., Asaka, I., Aoi, T., Watanabe, A., Yamada, Y., Morizane, A., Takahashi, J., Ayaki, T., Ito, H., Yoshikawa, K., Yamawaki, S., Suzuki, S., Watanabe, D., Hioki, H., Kaneko, T., Makioka, K., Okamoto, K., Takuma, H., Tamaoka, A., Hasegawa, K., Nonaka, T., Hasegawa, M., Kawata, A., Yoshida, M., Nakahata, T., Takahashi, R., Marchetto, M. C. N., Gage, F. H., Yamanaka, S., and Inoue, H
  • Journal Title: Sci. Transl. Med. Volume: 4 Issue: 145 Pages: 1-8
  • DOI: 10.1126/scitranslmed.3004052
  • Peer Reviewed
• [Presentation] パーキンソン病に対するiPS細胞を用いた細胞移植治療 (2014)
  • Author(s): 森実飛鳥
  • Organizer: 第32回日本こども病院神経外科医会
  • Place of Presentation: 静岡
  • Year and Date: 2014-11-22
  • Invited
• [Presentation] パーキンソン病に対する細胞移植治療～iPS細胞の臨床応用～ (2014)
  • Author(s): 森実飛鳥
  • Organizer: 「細胞を創る」研究会7.0
  • Place of Presentation: 東京
  • Year and Date: 2014-11-14
  • Invited
• [Presentation] Immune response in the brain after transplantation of the neural cells derived from induced pluripotent stem cells (2014)
  • Author(s): Asuka Morizane
  • Organizer: The 10th Annual Meeting of Korean Society of Stem Cell Research
  • Place of Presentation: 韓国ソウル
  • Year and Date: 2014-08-28
  • Invited
• [Presentation] シヌクレイノパチーの病態・治療研究最前線 (2014)
  • Author(s): 森実飛鳥
  • Organizer: J-CAN 2014
  • Place of Presentation: 東京
  • Year and Date: 2014-08-23
  • Invited
• [Presentation] Autologous transplantation of iPS cell-derived neurons to the brain of non-human primate (2014)
  • Author(s): Asuka Morizane, Daisuke Doi, Tetsuhiro Kikuchi and Jun Takahashi
  • Organizer: The 12th Stem Cell Research Symposium
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-30
  • Invited
• [Presentation] Autologous Transplantation with iPSC-derived Neurons is Immunologically Beneficial even in the Brain (2014)
  • Author(s): Asuka Morizane, Daisuke Doi, Tetsuhiro Kikuchi, Keisuke Okita, Akitsu Hotta, Toshiyuki Kawasaki, Hirotaka Onoe, Takashi Shiina , Shinya Yamanaka, and Jun Takahashi
  • Organizer: The 7th Takeda Science Foundation Symposium on PharmaSciences,
  • Place of Presentation: Osaka, Japan
• [Presentation] iPS細胞由来ドパミン神経を用いた神経細胞の自家移植 (2014)
  • Author(s): 森実飛鳥
  • Organizer: 第９回京大病院iPS細胞・再生医学研究会
  • Place of Presentation: 京都
  • Invited
• [Presentation] 合成ラミニンを使用したiPS細胞からのドパミン神経分化誘導 (2014)
  • Author(s): 森実飛鳥
  • Organizer: 大阪大学蛋白研セミナー
  • Place of Presentation: 大阪
  • Invited
• [Presentation] Autologous Transplantation of Induced Pluripotent Stem Cell-Derived Neurons Causes Minimum Immune Reaction in the Brain of Non-Human Primate. (2013)
  • Author(s): Morizane A, Doi D, Kikuchi T, Okita K, Hotta A, Kawasaki T, Onoe H, Shiina T, Takahashi J
  • Organizer: ISSCR 11th Annual Meeting
  • Place of Presentation: Boston, USA
• [Presentation] Transplantation of autologous neural cells derived from induced pluripotent stem cells (iPSCs) to the brain of non-human primate (2013)
  • Author(s): Morizane A
  • Organizer: 2013 CABX Workshop and International Symposium
  • Place of Presentation: Jeju, Korea
  • Invited
• [Presentation] ｉPS細胞を用いた自家移植の有効性～カニクイザル脳内神経細胞移植の系を用いて～ (2013)
  • Author(s): 森実飛鳥、土井大輔、菊地哲広 他
  • Organizer: 第１２回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Autologous/Allogenic transplantation of neurons derived from iPSCs into monkey brain (2013)
  • Author(s): Asuka Morizane
  • Organizer: CiRA International Symposium 2013
  • Place of Presentation: 京都大学
  • Invited
• [Presentation] サルiPS細胞による神経分化誘導：自家移植モデルを目指して (2012)
  • Author(s): 森実飛鳥、土井大輔、菊地哲、高橋 淳
  • Organizer: 第11回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜
• [Presentation] Differentiation from primate induced pluripotent stem cells designed for an auto-grafting model system. (2012)
  • Author(s): Morizane A, Okita K, Doi D,et al.
  • Organizer: ISSCR 10th Annual Meeting
  • Place of Presentation: パシフィコ横浜
• [Presentation] サルiPS細胞由来神経の自家移植 (2012)
  • Author(s): 森実飛鳥、土井大輔、菊地哲、他
  • Organizer: 日本脳神経外科学会第71回学術総会
  • Place of Presentation: リーガロイヤルホテル大阪
• [Book] 先端医療シリーズ45 臨床医のための最新脳神経外科 (2014)
  • Author(s): 森実飛鳥、高橋 淳 (分担執筆)
  • Total Pages: 4
  • Publisher: 先端医療技術研究所
• [Remarks] 京都大学iPS細胞研究所 臨床応用研究部門 神経再生研究分野
  • URL: http://www.frontier.kyoto-u.ac.jp/ca01/index.html
• [Remarks] 京都大学再生医科学研究所 生体修復応用分野
  • URL: http://www.frontier.kyoto-u.ac.jp/ca01/index.html