Development of a Lung Regenaration Model Using Autologous Cells

• Project/Area Number: 17H06274
• Research Category: Grant-in-Aid for Challenging Research (Pioneering)
• Allocation Type: Single-year Grants
• Research Field: Surgery of the organs maintaining homeostasis and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Kitano Kentaro 東京大学, 医学部附属病院, 助教 (70647073)
• Co-Investigator(Kenkyū-buntansha): 長山 和弘 東京大学, 医学部附属病院, 助教 (00647935) ; 安樂 真樹 東京大学, 医学部附属病院, 特任研究員 (70598557) ; 垣見 和宏 東京大学, 医学部附属病院, 特任教授 (80273358) ; 中島 淳 東京大学, 医学部附属病院, 教授 (90188954) ; 似鳥 純一 東京大学, 医学部附属病院, 助教 (40424486)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000); Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000); Fiscal Year 2017: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
• Keywords: 再生医療 / 脱細胞化 / 肺再生 / 大動物モデル / 肺移植 / 細胞分離 / 呼吸器外科 / 臓器再生 / 脱細胞 / 動物モデル

Outline of Final Research Achievements

The aim of this study is to evaluate feasibility and in vivo function of bioengineered lung transplanted in the porcine model. We utilized decellularization technique. Porcine decellularized lung scaffolds were seeded with recipient-derived porcine auto-cells collected from lung tissue obtained by pulmonary wedge resection. The resulting grafts were unilaterally transplanted into porcine recipients. The pigs transplanted with bioengineered lungs survived for 2 hours. The oxygen gas exchange of bioengineered lung transplant was comparable to that of allograft transplant.

Academic Significance and Societal Importance of the Research Achievements

慢性閉塞性肺疾患や間質性肺炎などの末期肺疾患は依然として生命予後の悪い疾患である。同種他家肺移植は末期肺疾患に対して唯一の望みのある治療法であるが、拒絶などの合併症の問題がある。そこで患者自身の細胞をもとに再生肺を構築し、それを移植することで末期肺疾患を克服できると考えた。本研究はブタという大動物モデルを用いて、自家細胞由来の再生肺を構築し、実際にレシピエントに肺移植を行ってガス交換能を検証した。本研究は、今後の肺再生研究において必要な課題を提示した。

Research Products

• [Journal Article] Transplantation of Bioengineered Lungs Created From Recipient-Derived Cells Into a Large Animal Model (2020)
  • Author(s): Yanagiya Masahiro、Kitano Kentaro、Yotsumoto Takuma、Asahina Hiromichi、Nagayama Kazuhiro、Nakajima Jun
  • Journal Title: Seminars in Thoracic and Cardiovascular Surgery Volume: - Issue: 1 Pages: 263-271
  • DOI: 10.1053/j.semtcvs.2020.03.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effect of normal saline flush injection into a bronchus on lung decellularization (2019)
  • Author(s): Yanagiya Masahiro、Kitano Kentaro、Yotsumoto Takuma、Takai Daiya、Asahina Hiromichi、Nagayama Kazuhiro、Nakajima Jun
  • Journal Title: Journal of Thoracic Disease Volume: 11 Issue: 12 Pages: 5321-5327
  • DOI: 10.21037/jtd.2019.11.59
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Transplantation of bioengineered lungs created from recipient-derived cells in a large-animal model (2019)
  • Author(s): Masahiro Yanagiya, Kentaro Kitano, Takuma Yotsumoto, Kazuhiro Nagayama, Masaaki Sato, Jun Nakajima
  • Organizer: The 27th European Conference on General Thoracic Surgery
  • Int'l Joint Research
• [Presentation] 肺再生モデル作成に必要なブタ気道上皮前駆細胞の分離培養の確立 (2018)
  • Author(s): 柳谷昌弘 北野健太郎 長山和弘 中島淳
  • Organizer: 第71回 日本胸部外科学会定期学術集会
• [Presentation] Effect of normal saline flush injection into bronchus on lung decellularization (2018)
  • Author(s): Masahiro Yanagiya, Kentaro Kitano, Takuma Yotsumoto, Kazuhiro Nagayama, Jun Nakajima
  • Organizer: 27th The Asian Society for Cardiovascular and Thoracic Surgery
  • Int'l Joint Research
• [Presentation] 肺再生モデル作成に必要な、ブタ肺血管内皮前駆細胞の分離培養の確立 (2018)
  • Author(s): 柳谷昌弘 北野健太郎 長山和弘 中島淳
  • Organizer: 第119回 日本外科学会定期学術集会