Reconstruction of liver from arranged-hepatocytes/liver sinusoidal endothelial cells/cholangiocytes tissues
| Project/Area Number |
19H04445
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 90110:Biomedical engineering-related
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| Research Institution | Kyushu University |
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Principal Investigator |
SAKAI Yusuke 九州大学, 工学研究院, 助教 (10608904)
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| Co-Investigator(Kenkyū-buntansha) |
江口 晋 長崎大学, 医歯薬学総合研究科(医学系), 教授 (80404218)
中澤 浩二 北九州市立大学, 国際環境工学部, 教授 (00304733)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Keywords | 肝細胞 / 内皮細胞 / 胆管 / 類洞 / 肝再生医療 |
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| Outline of Research at the Start |
細胞の立体組織化は再生医療等に有望なアプローチであるが、肝小葉構造を再現することは困難を極めている。本研究では、初代肝細胞、類洞内皮細胞、胆管細胞を立体配置して“効率的な物質交換を実現する肝細胞／類洞索状構造”と“胆汁排泄を担う胆管”を有するヒト肝臓を立体再構築する基盤技術を確立する。ヒト初代肝細胞と類洞内皮細胞の二次元配列・三次元培養とリプログラミングに基づく肝毛細胆管－肝内胆管構造・機能の再構築技術を融合し、肝細胞／類洞内皮細胞（類洞）／胆管細胞（胆管）配列組織（A-HECT）を作製する。肝再生刺激を誘発し得るマウスにA-HECTを移植し、機能的な類洞及び胆管構築を実現する。
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| Outline of Final Research Achievements |
Hepatocytes/endothelial cell tissue arranged in a network was prepared using a multi-pored silicone film (MPSF). Rat primary hepatocytes cultured with arranged human umbilical vein endothelial cells (HUVECs) or liver sinusoidal endothelial cells (hLSECs) showed highly expressed liver-specific genes. The tissue maintained its functions subcutaneously in mice, suggesting the reconstruction of capillaries with luminal structure. A method for efficiently producing bile duct tissue from hepatic progenitor cells were established. The junction between bile duct tissue and hepatic bile canaliculus were demonstrated. By combining these techniques, we will establish an innovative method for creating a “liver” with sinusoid and bile duct structures.
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| Academic Significance and Societal Importance of the Research Achievements |
肝小葉に代表される秩序立った構造と多岐にわたる機能を持つ肝臓の再構築は、困難を極めている。本研究では、初代肝細胞、類洞内皮細胞、胆管細胞を立体配置して“効率的な物質交換を実現する肝細胞／類洞索状構造”と“胆汁排泄を担う胆管”の複合組織を実現する世界初の技術を確立した。再生医療や薬物代謝アッセイ等に有望な肝組織を作製する技術であり、ドナー不足の解消や薬剤代謝予測に繋がることから社会的な意義も大きい。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Bile duct reconstruction using scaffold-free tubular constructs created by Bio-3D printer.2021
Author(s)
Takashi Hamada, Anna Nakamura, Akihiko Soyama, Yusuke Sakai, Takayuki Miyoshi, Shun Yamaguchi, Masaaki Hidaka, Takanobu Hara, Tota Kugiyama, Mitsuhisa Takatsuki, Akihide Kamiya, Koichi Nakayama, Susumu Eguchi.
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Journal Title
Regenerative Therapy
Volume: 16
Pages: 81-89
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] The successful induction of human liver progenitor cells by low-molecular compounds from mature hepatocytes in a severely cirrhotic liver undergoing liver transplantation2021
Author(s)
Miyoshi T, Hidaka M, Miyamoto D, Murakami S, Huang Y, Sakai Y, Kugiyama T, Hara T, Torashima Y, Ochiya T, Eguchi S
Organizer
第23回日本肝胆膵外科学会学術集会
Related Report
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