Regenerative medicine for esophagus using a scaffold-free structure created with bio-three-dimensional printing technology

• Project/Area Number: 17K10595
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Nagasaki University
• Principal Investigator: TANIGUCHI Daisuke 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (20773758)
• Co-Investigator(Kenkyū-buntansha): 國崎 真己 長崎大学, 病院(医学系), 助教 (10533747) ; 土谷 智史 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (30437884) ; 中山 功一 佐賀大学, 医学部, 教授 (50420609) ; 永安 武 長崎大学, 医歯薬学総合研究科(医学系), 教授 (80284686) ; 松本 桂太郎 長崎大学, 医歯薬学総合研究科(医学系), 講師 (80404268)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 移植・再生医療 / 移植医療 / 再生医療 / 食道再生 / 再生医学 / 外科

Outline of Final Research Achievements

Various strategies have been attempted to replace esophageal defects， however， these methods have not yet reached clinical application. In this research project， we developed a scaffold-free structure with a mixture of cell types using bio-3D printing technology. The artificial esophageal-like tube structures were prepared by bio-3D printing， then structures were transplanted into rats as esophageal grafts. Mechanical and histochemical assessment of the structures were performed. The scaffold-free structures had sufficient strength for transplantation between the esophagus and stomach using silicon stents. The structures were maintained in vivo for 30 days after transplantation. Flat epithelium extended and covered the inner surface of the lumen. Food had also passed through the structure. These results suggested that the esophagus-like scaffold-free tubular structures created using bio-3D printing could hold promise as a substitute for the repair of esophageal defects.

Academic Significance and Societal Importance of the Research Achievements

細胞のみからなる人工臓器による再生医療は，自己細胞やiPS細胞を利用できる点や異物を必要としない点などから理想的である．我々は，細胞凝集現象を応用したバイオ３Dプリンターを用いた食道再生の研究を行った．人工食道を用いた食道の再生医療は，成人，小児双方において，現治療の代替医療として重要な意味を持つ．これを治療に用いることができれば，食道疾患治療において，大きなオプションを持つことになるとともに，再生医療に画期的な変革をもたらすことができると考える．今回の研究では，人工食道のラットへの移植へ成功しており，食道再生の第一歩としての学術的意義があると考えられる．

Research Products

• [Journal Article] Regeneration of esophagus using a scaffold-free biomimetic structure created with bio-three-dimensional printing. (2019)
  • Author(s): Takeoka Y, Matsumoto K, Taniguchi D, Tsuchiya T, Machino R, Moriyama M, Oyama S, Tetsuo T, Taura Y, Takagi K, Yoshida T, Elgalad A, Matsuo N, Kunizaki M, Tobinaga S, Nonaka T, Hidaka S, Yamasaki N, Nakayama K, Nagayasu T.
  • Journal Title: PLoS One. Volume: 14 Issue: 3 Pages: e0211339-e0211339
  • DOI: 10.1371/journal.pone.0211339
  • NAID: 120006987768
  • Peer Reviewed
• [Presentation] バイオ3Dプリンティングを用いた細胞のみからなる人工食道作製の試み (2017)
  • Author(s): 武岡陽介
  • Organizer: 第17回日本再生医療学会総会