title: Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes.
abstract: 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.
authors.affiliation: Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academic of Sciences, Shanghai 200031, China.
authors.forename: Yimeng
authors.initials: Y
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academic of Sciences, Shanghai 200031, China.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Hucheng
authors.initials: H
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academic of Sciences, Shanghai 200031, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academic of Sciences, Shanghai 200031, China.|School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Huang
authors.affiliation: Center for Drug Safety Evaluation and Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Ni
authors.affiliation: State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academic of Sciences, Shanghai 200031, China.
authors.forename: Ludi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Haozhen
authors.initials: H
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, Shanghai, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Tian
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academic of Sciences, Shanghai 200031, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Center for Drug Safety Evaluation and Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Guoyu
authors.initials: G
authors.lastname: Pan
authors.affiliation: Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academic of Sciences, Shanghai 200031, China.|School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Hui
mesh_terms: D000418:Albumins / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D002460:Cell Line; D022781:Hepatocytes / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D017114:Liver Failure, Acute / Q000378:metabolism* / Q000503:physiopathology*; D019164:Liver, Artificial; D013552:Swine
chemical_list: D000418:Albumins; D000641:Ammonia; D001663:Bilirubin