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

• Published in: Regenerative therapy Vol. 10; pp. 127 - 133
• Main Authors: Minami, Takahito, Ishii, Takamichi, Yasuchika, Kentaro, Fukumitsu, Ken, Ogiso, Satoshi, Miyauchi, Yuya, Kojima, Hidenobu, Kawai, Takayuki, Yamaoka, Ryoya, Oshima, Yu, Kawamoto, Hiroshi, Kotaka, Maki, Yasuda, Katsutaro, Osafune, Kenji, Uemoto, Shinji
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2019; Japanese Society for Regenerative Medicine; Elsevier
• Subjects: Artificial liver; Decellularized liver; Hepatocyte; Human iPSC; Original; Recellularization; Artificial liver; Decellularized liver; Hepatocyte; Recellularization; Human iPSC
• ISSN: 2352-3204; 2352-3204
• DOI: 10.1016/j.reth.2019.03.002

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. 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. 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. Novel hybrid artificial livers using hiPSCs and rat decellularized liver scaffolds were successfully generated, which possessed human hepatic functions. •Human iPSC-derived hepatocytes were engrafted in a rat decellularized liver scaffold.•The recellularized liver expressed human liver-related markers ALB and CYP3A4.•The recellularized liver scaffold secreted human albumin.•This novel model shows potential for artificial whole liver transplantation.