Study of bone regeneration using iPS cells

• Project/Area Number: 16K11747
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Kyoto University
• Principal Investigator: Koyama Noriaki 京都大学, 医学研究科, 客員研究員 (30599931)
• Co-Investigator(Kenkyū-buntansha): 別所 和久 京都大学, 医学研究科, 教授 (90229138)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: iPS細胞 / 培養上清 / 骨軟骨再生 / 骨形成 / 骨再生 / ES細胞 / SHED / BMMSC / 再生医療

Outline of Final Research Achievements

Regeneration and functional recovery of bone tissue in the oral cavity area is a very important task. Although the standard treatment method is autologous bone grafting, the invasiveness of the bone collection site is large, the collection amount is also limited, and a new treatment method is strongly desired. This time, we conducted research on bone regeneration using iPS cells.
The culture supernatant derived from iPS cells was used as a cell source for bone regeneration, mixed with atelocollagen, and transplanted to a rat bone defect site. Evaluation of the tissue obtained after sacrifice after transplantation showed that bone formation was observed at the bone grafting site, suggesting the possibility of promoting bone regeneration.
It was suggested that bone regeneration using iPS-derived osteogenic cells and their culture supernatants could be a novel minimally invasive bone regeneration treatment.

Academic Significance and Societal Importance of the Research Achievements

骨再生は口腔領域において長年にわたる課題であるが、大きな骨欠損に対して回復する手段の構築に難渋している。体性幹細胞を用いた従来の骨再生療法は、修復量に制限が生じ、そのため適応症例が限られていた。
本研究により、iPS細胞を用いて生体の発生生理に準じた培養方法にて得られた細胞を利用して骨形成を行うことは、将来の再生医療の可能性を見据えた上で大変有効であると考えられる。iPS由来骨形成性細胞およびその培養上清液を用いた骨再生が可能になれば、侵襲が限りなく小さく、あらかじめ計画的に作製・保存・準備することが可能であり、大量供給に対応することが可能になる点は非常に有意義であると予想される。

Research Products

• [Journal Article] Direct evidence for the age-dependent demise of GNAS -mutated cells in oral fibrous dysplasia (2018)
  • Author(s): Isobe Yu、Takahashi Katsu、Kiso Honoka、Nakao Kazumasa、Ikeno Masayuki、Koyama Noriaki、Sugai Manabu、Shimizu Akira、Haga Hironori、Bessho Kazuhisa
  • Journal Title: Archives of Oral Biology Volume: 93 Pages: 133-140
  • DOI: 10.1016/j.archoralbio.2018.05.018
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Circulatory CNP Rescues Craniofacial Hypoplasia in Achondroplasia (2017)
  • Author(s): Yamanaka S.、Nakao Kazumasa、Koyama N.、Isobe Y.、Ueda Y.、Kanai Y.、Kondo E.、Fujii T.、Miura M.、Yasoda A.、Nakao Kazuwa、Bessho K.
  • Journal Title: Journal of Dental Research Volume: 96 Issue: 13 Pages: 1526-1534
  • DOI: 10.1177/0022034517716437
  • Peer Reviewed / Open Access
• [Journal Article] A novel therapeutic strategy for midfacial hypoplasia using the CNP/GC-B system. (2017)
  • Author(s): Nakao K, Yasoda A, Okubo Y, Yamanaka S, Koyama N, Osawa K, Isobe Y, Ikeno M, Fujii T, Miura M, Bessho K.
  • Journal Title: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Volume: 29 Issue: 1 Pages: 10-16
  • DOI: 10.1016/j.ajoms.2016.07.007
  • Peer Reviewed