Engineering three dimensional hepatic tissues with perfusable vasculatures

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H04573
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biofunction/Bioprocess
• Research Institution: Yokohama National University
• Principal Investigator: FUKUDA Junji 横浜国立大学, 大学院工学研究院, 教授 (80431675)
• Co-Investigator(Kenkyū-buntansha): 丸尾 昭二 横浜国立大学, 大学院工学研究院, 教授 (00314047) ; 渡邉 昌俊 三重大学, 医学系研究科, 教授 (90273383)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 再生医療 / 肝臓 / 血管 / 電気化学 / オリゴペプチド

Outline of Final Research Achievements

The lack of fabrication strategy of perfusable vascular networks is a fundamental barrier to engineer thick and cell-dense tissues and organs for regenerative medicine. In this study, we propose a rapid engineering approach of spatially-aligned and perfusable macrovasculatures. We designed an electrochemically cleavable oligopeptide which can be used for cell transfer from a culture surface to a hydrogel. Using this oligopeptide on a needle, macrovasculatures whose internal surface was covered with endothelial cells were fabricated in a hydrogel. The endothelial cells transferred were then migrated and formed luminal structures in the hydrogel, leading to formation of perfusable macro- and micro-vascular networks. Furthermore, by encapsulating iPS-derived hepatic endoderm spheroids between the macrovasculatures, functional liver tissues with vascular networks were induced. This simple and versatile approach promises various applications for engineering three-dimensional thick tissues.

Free Research Field

生物工学

Academic Significance and Societal Importance of the Research Achievements

再生医療の分野では、送液可能な血管構造を構築する技術の確立が不十分であったため、作製できる移植用組織のサイズは酸素の拡散範囲という制限がかかり、かなり薄いものに限られていた。本研究では、ハイドロゲル内に細胞を適切に配置することで、細胞の自己組織化により機能的な組織が形成されることを示した。また、今後この手法をさらに発展させ、より細胞密度および血管密度の高い機能的な立体組織を作製できれば、直接血管を吻合して移植可能な移植用臓器の作製が可能となり、肝臓に限らず様々な臓器の再生医療につながると考えられる。