TY - JOUR
T1 - Novel hybrid three-dimensional artificial liver using human induced pluripotent stem cells and a rat decellularized liver scaffold
AU - Minami, Takahito
AU - Ishii, Takamichi
AU - Yasuchika, Kentaro
AU - Fukumitsu, Ken
AU - Ogiso, Satoshi
AU - Miyauchi, Yuya
AU - Kojima, Hidenobu
AU - Kawai, Takayuki
AU - Yamaoka, Ryoya
AU - Oshima, Yu
AU - Kawamoto, Hiroshi
AU - Kotaka, Maki
AU - Yasuda, Katsutaro
AU - Osafune, Kenji
AU - Uemoto, Shinji
N1 - Funding Information:
This work was supported by Japan Society for the Promotion of Science (Grant Number: 16H05489 ).
Publisher Copyright:
© 2019 The Japanese Society for Regenerative Medicine
PY - 2019/6
Y1 - 2019/6
N2 - 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 CO 2 (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.
AB - 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 CO 2 (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.
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U2 - 10.1016/j.reth.2019.03.002
DO - 10.1016/j.reth.2019.03.002
M3 - Article
AN - SCOPUS:85063445896
VL - 10
SP - 127
EP - 133
JO - Regenerative Therapy
JF - Regenerative Therapy
SN - 2352-3204
ER -