Regenerative Therapy (Jun 2019)

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

  • Takahito Minami,
  • Takamichi Ishii,
  • Kentaro Yasuchika,
  • Ken Fukumitsu,
  • Satoshi Ogiso,
  • Yuya Miyauchi,
  • Hidenobu Kojima,
  • Takayuki Kawai,
  • Ryoya Yamaoka,
  • Yu Oshima,
  • Hiroshi Kawamoto,
  • Maki Kotaka,
  • Katsutaro Yasuda,
  • Kenji Osafune,
  • Shinji Uemoto

Journal volume & issue
Vol. 10
pp. 127 – 133

Abstract

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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. Keywords: Decellularized liver, Recellularization, Human iPSC, Hepatocyte, Artificial liver