Fabrication of human liver with mimicking hepatic lobule structures by alternately-arranged human hepatocyte/endotherial cell tissue transplantation

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05908
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Nagasaki University
• Principal Investigator: SAKAI Yusuke 長崎大学, 医歯薬学総合研究科(医学系), 助教 (10608904)
• Research Collaborator: EGUCHI Susumu ; NAKAZAWA Kohji ; KOIKE Makiko ; YAMANOUCHI Kosho ; SOYAMA Akihiko ; HIDAKA Masaaki ; TAKATSUKI Mitsuhisa
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 肝細胞 / 内皮細胞 / 肝臓 / アレイ化 / 再生医療 / 管腔

Outline of Final Research Achievements

Alternately-arranged human hepatocyte/ endothelial cell tissue (AHET) could contribute to oxygen supply, survival, three-dimensional organization, and maintenance of liver-specific functions. In this study, we aimed to fabricate AHET by using micropatterning technology and cell sheet engineering.
Multi-pored silicone film (MPSF) were prepared using microchannels. Human primary hepatocytes adhered to the perforated region of MPSF. The hepatocytes densely aggregated and were patterned. The hepatocytes were cocultured with HUVEC, and alternately-arranged human hepatocyte/ endothelial cell was generated. hADSC supported the formation of the luminal-like structure of HUVEC. AHET could be harvested and was an implantable tissue.

Free Research Field

再生医工学

Academic Significance and Societal Importance of the Research Achievements

これまでに、規則的な血管網を持つ細胞だけで構成された移植用組織体の作製は困難であった。本研究では、肝小葉構造に基づき規則的に内皮細胞を配置すると共に、細胞のみで管腔構造を形成させる技術を確立した。ヒト初代肝細胞－内皮細胞索状組織（AHET）は、移植用の組織体として新しい移植医療に応用し得る可能性を秘めている。さらに、本技術を基盤として、他の機能性細胞（膵島細胞等）への迅速な応用が考え得る。これらのことから、次世代の移植再生医療技術として波及効果は多大である。