A Producing of artificial pleura based on tissue engineering

Research Project

Project/Area Number	18K08776
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55040:Respiratory surgery-related
Research Institution	Hirosaki University
Principal Investigator	Kimura Daisuke 弘前大学, 医学研究科, 准教授 (70396406)
Project Period (FY)	2018-04-01 – 2023-03-31
Project Status	Completed (Fiscal Year 2022)
Budget Amount *help	¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000) Fiscal Year 2020: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000) Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Keywords	再生医療 / テイッシュエンジニアリング / 中皮細胞 / 人工胸膜 / 積層培養 / 肺瘻 / PGAナノファイバー / 胸膜中皮 / ティッシュエンジニアリング / 人工臓器 / 細胞選択
Outline of Final Research Achievements	The efficacy of mesothelial cell-based pleural prostheses was evaluated in a rat with pleural diffect. Two types of pleural prostheses, one with a single layer of mesothelium and the other with only one layer of mesothelium, were prepared on collagen-coated PGA nanofiber sheets with four layers of fibroblasts and cultured for 5 days. Scanning electron microscopy revealed that the pleura consisting of one layer of pleural mesothelial cells plus four layers of pulmonary fibroblasts had tighter intercellular contacts and a more cobblestone-like arrangement of cells and more microvilli on the surface than the pleura made of only one layer of pleural mesothelial cells. The artificial pleura was transplanted into a rat pleural defect model, and the graft was harvested and observed for viability. Immunostaining showed thinning of the transplanted area and mesothelial cell growth, indicating that the artificial pleura was effective in the pleural defect model.
Academic Significance and Societal Importance of the Research Achievements	呼吸器外科手術患者において、肺切除後の肺瘻は入院期間延長のみならず、膿胸などの合併症を引き起こす可能性がある。慢性閉塞性肺疾患や間質性肺炎などの患者は肺瘻遷延を引き起こしやすく、今後も肺瘻の発生数は増加することが予想される。また、移植肺の代替となるような人工肺の開発研究が将来進めば、それを被覆する人工胸膜も必要となると考える。本研究においては移植部の菲薄化とそれに伴う中皮細胞の生着を認め、作成した人工胸膜は胸膜欠損部の修復に有効であり、将来的に人工胸膜移植が胸膜欠損の一手段となる可能性が示唆された。