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

利用人类诱导性多能干细胞和大鼠脱细胞肝支架的新型混合三维人工肝

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作者: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

Conclusion

Novel hybrid artificial livers using hiPSCs and rat decellularized liver scaffolds were successfully generated, which possessed human hepatic functions.

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.

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