Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes

Acute liver failure （ALF） is a life-threatening illness. The extracorporeal cell-based bioartiflcial liver （BAL） system could bridge liver transplantation and facilitate liver regeneration for ALF patients by providing met- abolic detoxification and synthetic functions. Previous BAL systems, based o...

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Bibliographic Details
Published in:Cell research 2016-02, Vol.26 (2), p.206-216
Main Authors: Shi, Xiao-Lei, Gao, Yimeng, Yan, Yupeng, Ma, Hucheng, Sun, Lulu, Huang, Pengyu, Ni, Xuan, Zhang, Ludi, Zhao, Xin, Ren, Haozhen, Hu, Dan, Zhou, Yan, Tian, Feng, Ji, Yuan, Cheng, Xin, Pan, Guoyu, Ding, Yi-Tao, Hui, Lijian
Format: Article
Language:English
Subjects:
Albumins - metabolism
Ammonia - metabolism
Animals
Bilirubin - metabolism
Cell Line
Hepatocytes - metabolism
Hepatocytes - physiology
Humans
Liver Failure, Acute - metabolism
Liver Failure, Acute - physiopathology
Liver, Artificial
Original
Swine
人肝细胞
急性
植入
猪
生物人工肝
肝功能衰竭
装置
诱导
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Summary:Acute liver failure （ALF） is a life-threatening illness. The extracorporeal cell-based bioartiflcial liver （BAL） system could bridge liver transplantation and facilitate liver regeneration for ALF patients by providing met- abolic detoxification and synthetic functions. Previous BAL systems, based on hepatoma cells and non-human hepatocytes, achieved limited clinical advances, largely due to poor hepatic functions, cumbersome preparation or safety concerns of these cells. We previously generated human functional hepatocytes by lineage conversion （hiHeps）. Here, by improving functional maturity of hiHeps and producing hiHeps at clinical scales （3 billion cells）, we developed a hiHep-based BAL system （hiHep-BAL）. In a porcine ALF model, hiHep-BAL treatment restored liver functions, corrected blood levels of ammonia and bilirubin, and prolonged survival. Importantly, human albumin and a-l-antitrypsin were detectable in hiHep-BAL-treated ALF pigs. Moreover, hiHep-BAL treatment led to attenuated liver damage, resolved inflammation and enhanced liver regeneration. Our findings indicate a promising clinical application of the hiHep-BAL system.
ISSN:1001-0602
1748-7838
DOI:10.1038/cr.2016.6