Development of bone-organod and its application for the research in bone diseases

• Project/Area Number: 17K19725
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Surgery related to the biological and sensory functions and related fields
• Research Institution: Kyoto University
• Principal Investigator: TOGUCHIDA JUNYA 京都大学, ウイルス・再生医科学研究所, 教授 (40273502)
• Co-Investigator(Kenkyū-buntansha): 吉富 啓之 京都大学, ウイルス・再生医科学研究所, 准教授 (50402920)
• Research Collaborator: ADACHI Taiji ; ALEV Cantas ; KAWAI Shunsuke ; NIWA Akira ; MATSUDA Shuichi
• Project Period (FY): 2017-06-30 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
• Keywords: オルガノイド / IPS細胞 / 骨改変 / 骨疾患 / iPS細胞 / 骨芽細胞 / 骨細胞 / 破骨細胞 / 骨組織

Outline of Final Research Achievements

We established a method to make bone-like nodules from human iPS cells within 10 days using retinoic acid signal, and observed this process by the time-lapse imaging. We also succeeded to visualize the differentiation process from osteoblasts to osteocytes using collagen gel culture system, and demonstrated that the induction method and experimental system are useful for disease-modeling and drug screening using patient-specific iPS cells of osteogenesis imperfecta.

Academic Significance and Societal Importance of the Research Achievements

学術的意義としては、骨代謝研究分野における新しいin vitroでの解析システムとして極めて有用なものである。社会的意義としては、難治性の骨疾患に対する病態解明から創薬へのプロセスに有用なものであり、有効な治療薬の無い疾患における患者の臨床病態の改善に貢献できる可能性がある。

Research Products

• [Journal Article] An mTOR Signaling Modulator Suppressed Heterotopic Ossification of?Fibrodysplasia Ossificans Progressiva (2018)
  • Author(s): Hino Kyosuke、Zhao Chengzhu、Horigome Kazuhiko、Nishio Megumi、Okanishi Yasue、Nagata Sanae、Komura Shingo、Yamada Yasuhiro、Toguchida Junya、Ohta Akira、Ikeya Makoto
  • Journal Title: Stem Cell Reports Volume: 11 Issue: 5 Pages: 1106-1119
  • DOI: 10.1016/j.stemcr.2018.10.007
  • Peer Reviewed / Open Access
• [Journal Article] Human Sox4 facilitates the development of CXCL13-producing helper T cells in inflammatory environments. (2018)
  • Author(s): Yoshitomi H, Kobayashi S, Miyagawa-Hayashino A, Okahata A, Doi K, Nishitani K, Murata K, Ito H, Tsuruyama T, Haga H, Matsuda S, Toguchida J
  • Journal Title: Nature Communications Volume: 9 Issue: 1 Pages: 3762-3762
  • DOI: 10.1038/s41467-018-06187-0
  • NAID: 120006523829
  • Peer Reviewed / Open Access
• [Journal Article] Modeling human somite development and fibrodysplasia ossificans progressiva with induced pluripotent stem cells (2018)
  • Author(s): Nakajima Taiki、Shibata Mitsuaki、Nishio Megumi、Nagata Sanae、Alev Cantas、Sakurai Hidetoshi、Toguchida Junya、Ikeya Makoto
  • Journal Title: Development Volume: 145 Issue: 16 Pages: 165431-165431
  • DOI: 10.1242/dev.165431
  • Peer Reviewed / Open Access
• [Journal Article] Prospective comparison of various radiological response criteria and pathological response to preoperative chemotherapy and survival in operable high-grade soft tissue sarcomas in the Japan Clinical Oncology Group study JCOG0304 (2018)
  • Author(s): Tanaka K, Ogawa G, Mizusawa J, Naka N, Kawai A, Takahashi M, Hiruma T, Matsumoto Y, Tsuchiya H, Nakayama R, Hatano H, Emori M, Hosaka M, Yoshida Y, Toguchida J, Abe S, Asanuma K, Yokoyama R, Hiraga H, Yonemoto T, Morii T, Matsumoto S, Nagano A, Yoshikawa H, Fukuda H, Ozaki T, Iwamoto Y.
  • Journal Title: World Journal of Surgical Oncology Volume: 16 Issue: 1 Pages: 160-160
  • DOI: 10.1186/s12957-018-1462-y
  • Peer Reviewed
• [Journal Article] Current state of therapeutic development for rare cancers in Japan, and proposals for improvement. (2018)
  • Author(s): Kawai A, Goto T, Shibata T, Tani K, Mizutani S, Nishikawa A, Shibata T, Matsumoto S, Nagata K, Narukawa M, Matsui S, Ando M, Toguchida J, Monden M, Heike T, Kimura S, Ueda R.
  • Journal Title: Cancer Sci. Volume: 109 Issue: 5 Pages: 1731-1737
  • DOI: 10.1111/cas.13568
  • Peer Reviewed / Open Access
• [Journal Article] Activin-A enhances mTOR signaling to promote aberrant chondrogenesis in fibrodysplasia ossificans progressiva. (2017)
  • Author(s): Hino K, Horigome K, Nishio M, Komura S, Nagata S, Zhao C, Jin Y, Kawakami K, Yamada Y, Ohta A, Toguchida J, Ikeya M.
  • Journal Title: J Clin Invest Volume: 127 Issue: 9 Pages: 3339-3352
  • DOI: 10.1172/jci93521
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Disease-specific iPS cells disclose the novel pathomechanism and provide a plattform for clinical trial for patients with FOP (2018)
  • Author(s): Toguchida J
  • Organizer: 12th International BMP Conferenc
  • Int'l Joint Research / Invited
• [Presentation] Enhanced mTOR signaling triggered by Activin-A in chondrogenesis of fibrodysplasia ossificans progressive (2018)
  • Author(s): Toguchida J, Hino K, Horigome K, Nishio M, Komura S,Nagata S, Jin Y, Kawakami K, Yamada Y, Ohta A, Ikeya M
  • Organizer: Orthopaedic Research Society
  • Int'l Joint Research
• [Presentation] 整形外科基礎領域へのiPS細胞の応用 (2018)
  • Author(s): 戸口田淳也
  • Organizer: 第33回日本整形外科学会基礎学術集会
  • Invited
• [Presentation] 疾患特異的iPS細胞を活用した病態解析から創薬 (2018)
  • Author(s): 戸口田淳也、日野恭介、池谷真、関口和也、金永輝、岡本健、吉富啓之、松田秀一
  • Organizer: 第36回日本骨代謝学会学術集会
• [Presentation] 疾患特異的iPS細胞を活用した病態解析から創薬 (2018)
  • Author(s): 戸口田淳
  • Organizer: 第91回日本生化学会大会
• [Presentation] 創薬応用を目指したヒトiPS細胞によるin vtiro骨形成過程再現系の構築 (2018)
  • Author(s): 川井俊介、吉富啓之、Cantas Aleve、永田早苗、西尾恵、須長純子、羽田匡孝、金永輝、玉置さくら、池谷真、吹上謙一、安達泰治、松田秀一、戸口田淳也
  • Organizer: 第17回日本再生医療学会総会
• [Presentation] Visualizing bone-like nodule formation using human induced pluripotent stem cells (2018)
  • Author(s): Kawai S、Yoshitomi H, Sunaga J, Alev C, Nagata S, Nishio M,Hada M, Fukiage K, Adachi T, Matsuda S, Toguchida T
  • Organizer: Orthopaedic Research Society 2018
  • Int'l Joint Research