Novel hybrid three-dimensional artificial liver using human induced pluripotent stem cells and a rat decellularized liver scaffold

• 石井, 隆道

  Department of Surgery, Graduate School of Medicine, Kyoto University･Center for iPS Cell Research and Application (CiRA), Kyoto University

• 小木曾, 聡

  Department of Surgery, Graduate School of Medicine, Kyoto University

• 小髙, 真希

  Department of Surgery, Graduate School of Medicine, Kyoto University･Japanese Red Cross Wakayama Medical Center

• 長船, 健二

  Department of Surgery, Graduate School of Medicine, Kyoto University

• 上本, 伸二

  Department of Surgery, Graduate School of Medicine, Kyoto University

• Miyauchi, Yuya

  Department of Surgery, Graduate School of Medicine, Kyoto University

• Kojima, Hidenobu

  Department of Surgery, Graduate School of Medicine, Kyoto University

• Kawai, Takayuki

  Department of Surgery, Graduate School of Medicine, Kyoto University

• Yamaoka, Ryoya

  Department of Surgery, Graduate School of Medicine, Kyoto University

• Oshima, Yu

  Department of Surgery, Graduate School of Medicine, Kyoto University

• Kawamoto, Hiroshi

  Department of Surgery, Graduate School of Medicine, Kyoto University

• Kotaka, Maki

  Center for iPS Cell Research and Application (CiRA), Kyoto University

• Yasuda, Katsutaro

  Department of Surgery, Graduate School of Medicine, Kyoto University･Center for iPS Cell Research and Application (CiRA), Kyoto University

• Osafune, Kenji

  Center for iPS Cell Research and Application (CiRA), Kyoto University

• Uemoto, Shinji

  Department of Surgery, Graduate School of Medicine, Kyoto University

抄録

Introduction: Liver transplantation is currently the only curative therapy for end-stage liver failure; however, establishment of alternative treatments is required owing to the serious donor organ shortage. Here, we propose a novel model of hybrid three-dimensional artificial livers using both human induced pluripotent stem cells (hiPSCs) and a rat decellularized liver serving as a scaffold. Methods: Rat liver harvesting and decellularization were performed as reported in our previous studies. The decellularized liver scaffold was recellularized with hiPSC-derived hepatocyte-like cells (hiPSC-HLCs) through the biliary duct. The recellularized liver graft was continuously perfused with the culture medium using a pump at a flow rate of 0.5 mL/min in a standard CO₂(5%) cell incubator at 37 °C. Results: After 48 h of continuous perfusion culture, the hiPSC-HLCs of the recellularized liver distributed into the parenchymal space. Furthermore, the recellularized liver expressed the albumin (ALB) and CYP3A4 genes, and secreted human ALB into the culture medium. Conclusion: Novel hybrid artificial livers using hiPSCs and rat decellularized liver scaffolds were successfully generated, which possessed human hepatic functions.

収録刊行物

• Regenerative therapy

  Regenerative therapy 10 127-133, 2019-06

  Elsevier BV

キーワード

• Decellularized liver
• Recellularization
• Human iPSC
• Hepatocyte
• Artificial liver

詳細情報

• CRID: 1050845763410758016
• NII論文ID: 120006719314
• ISSN: 23523204
• DOI: 10.1016/j.reth.2019.03.002
• HANDLE: 2433/243894
• Web Site: https://api.elsevier.com/content/article/PII:S235232041830107X?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S235232041830107X?httpAccept=text/plain
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
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  • Crossref
  • CiNii Articles
  • KAKEN