Development of extraoral periodontal tissue regeneration unit applying epigenetics to cell sheet engineering

• Project/Area Number: 18K17091
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57040:Regenerative dentistry and dental engineering-related
• Research Institution: Health Sciences University of Hokkaido
• Principal Investigator: YOSHIDA Koki 北海道医療大学, 歯学部, 助教 (30453260)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: エピジェネティクス / 歯周組織再生 / 口腔外歯周組織再生ユニット

Outline of Final Research Achievements

In this study, the preparation of new periodontal tissue on the extracted tooth outside the oral cavity was attempted.
First, the progenitor stem-like cells were prepared from the epithelial cell rests of Malassez derived from the periodontal ligament by stimulation with epigenetic agents, and co-cultured with dental pulp cells and umbilical vein endothelial cells for 1 week. The tendency of increasing mRNA expression of periodontal ligament-related genes and mesenchymal stem cell-related genes was observed, and the significant decreased levels of methylation were observed. These results indicated that epigenetic agents might induce the cell population similar to the periodontal ligament. The cell sheet was prepared from these cell populations and engrafted on the extracted root surface. Attempts were made to bond to the artificial bone filling material block, but good results were not obtained. Further investigations are needed in the future.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、歯周病で喪失される歯根膜を、歯髄細胞から作製する可能性を示した基礎的データであり、将来的に、治療困難な重度歯周炎の歯に対して、歯髄細胞を応用して新たな歯根膜を作製することで治療が可能になるかもしれないという、臨床に向けた学術的意義を有するものである。

Research Products

• [Journal Article] Direct reprogramming of epithelial cell rests of malassez into mesenchymal-like cells by epigenetic agents (2021)
  • Author(s): Yoshida Koki、Uehara Osamu、Kurashige Yoshihito、Paudel Durga、Onishi Aya、Neopane Puja、Hiraki Daichi、Morikawa Tetsuro、Harada Fumiya、Takai Rie、Sato Jun、Saitoh Masato、Abiko Yoshihiro
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 33473142-33473142
  • DOI: 10.1038/s41598-020-79426-4
  • Peer Reviewed / Open Access
• [Presentation] エピジェネティクスを応用した歯髄細胞の歯根膜様細胞への誘導 (2020)
  • Author(s): 大西 綾、吉田 光希、高橋 周平、Ariuntsetseg Khurelchuluun、Durga Paudel、平木 大地、森川 哲郎、原田 文也、植原 治、佐藤 惇、永易 裕樹、安彦 善裕
  • Organizer: 第33回日本口腔診断学会・第30回日本口腔内科学会・第13回日本口腔検査学会合同学術大会
• [Presentation] エピジェネティクスを応用したマラッセ上皮-間葉共培養システムの歯根膜特異的遺伝子の解析 (2019)
  • Author(s): 吉田光希、大西 綾、平木大地、Neopane Puja、Durga Paudel、Ariuntsetseg Khurelchuluun、森川哲郎、佐藤 惇、永易裕樹、安彦善裕
  • Organizer: 第12回日本口腔検査学会・第30回日本臨床口腔病理学会・第29回日本口腔内科学会・第32回日本口腔診断学会 合同学術大会
• [Presentation] エピジェネティクス修飾を応用したマラッセ上皮細胞の脱分化と骨分化誘導能の検討 (2018)
  • Author(s): 吉田光希、大西 綾、Paudel D、Neopane P、 平木大地、Adhikari BR、 森川哲郎、植原 治、佐藤 惇、西村学子、安彦善裕
  • Organizer: 第29回日本臨床口腔病理学会総会・第11回日本口腔検査学会総会共催学術大会
• [Remarks] 北海道医療大学歯学部生体機能・病態学系臨床口腔病理学分野ホームページ
  • URL: http://www3.hoku-iryo-u.ac.jp/courses/2/013/index.html