Regeneration of tracheal complex tissue using a scaffold which regulates distributions of cells and soluble factors

Research Project

Project/Area Number	17K16910
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Otorhinolaryngology
Research Institution	Kyoto University
Principal Investigator	Nakamura Ryosuke 京都大学, 医学研究科, 研究員 (40736708)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000) Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	気管 / 軟骨 / 上皮 / 再生 / 血管新生 / コラーゲン / ヘパリン / スキャフォールド
Outline of Final Research Achievements	We previously developed an artificial trachea, which induces regeneration of the epithelium, and have clinically used it. However, the artificial trachea cannot induce regeneration of the cartilage. Although a cartilage tissue is formed in an artificial trachea seeded with chondrocytes after implantation into a rabbit tracheal defect, the chondrocyte-seeded artificial trachea hampered epithelial regeneration. In this study, we used a novel scaffold, which resembles the shape and physical property of the cartilage, as a container of chondrocytes. Additionally, we made an artificial trachea, which consists of the chondrocyte-containing scaffold and a collagen sponge with heparin, to inhibit difusion of the angiostatic factors derived from chondrocytes. After implantation of the artificial trachea into a rabbit tracheal defect, cartilage with arch-like shape was formed to cover the defect. Epithelial regeneration on the artificial trachea was relatively fast.
Academic Significance and Societal Importance of the Research Achievements	本研究では気管再生医療における軟骨再生技術を発展させ得る知見が得られた。これまで用いられてきた人工気管は、空気の通り道として重要な気管の筒状構造を十分に維持するためにポリプロピレンを用いてきた。ポリプロピレンは形状が固定されているために、小児には使用できず、先天奇形による気管狭窄等を治療することができない。動物実験では、軟骨細胞移植によって気管軟骨再生を可能とする技術が示されているが、軟骨細胞由来の因子は血管等の組織形成を阻害するという課題が存在していた。本研究で得られた結果は、軟骨細胞移植の負の要素を改善し、軟骨と他組織の再生を両立するための技術を提案している。