Volume 26, No 2, Feb 2016

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 26 Issue 2, February 2016: 206-216   |  Open Access

ORIGINAL ARTICLES

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

Xiao-Lei Shi^1,*, Yimeng Gao^2,*, Yupeng Yan^2,*, Hucheng Ma^1,*, Lulu Sun^2,*, Pengyu Huang^2,3,*, Xuan Ni⁴, Ludi Zhang², Xin Zhao¹, Haozhen Ren¹, Dan Hu⁵, Yan Zhou⁵, Feng Tian⁶, Yuan Ji⁶, Xin Cheng², Guoyu Pan⁴, Yi-Tao Ding¹ and Lijian Hui^2,3

¹Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China
²State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academic of Sciences, Shanghai 200031, China
³School of Life Science and Technology, ShanghaiTech University, Shanghai, China
⁴Center for Drug Safety Evaluation and Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
⁵State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, Shanghai, China
⁶Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China Correspondence: Lijian Hui, E-mail: ljhui@sibcb.ac.cn; Yi-Tao Ding, E-mail: yitaoding@hotmail.com; Guoyu Pan,(gypan@cdser.simm.ac.cn)

Acute liver failure (ALF) is a life-threatening illness. The extracorporeal cell-based bioartificial liver (BAL) system could bridge liver transplantation and facilitate liver regeneration for ALF patients by providing metabolic 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 α-1-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.

10.1038/cr.2016.6

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