Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes. 2016

Xiao-Lei Shi, and Yimeng Gao, and Yupeng Yan, and Hucheng Ma, and Lulu Sun, and Pengyu Huang, and Xuan Ni, and Ludi Zhang, and Xin Zhao, and Haozhen Ren, and Dan Hu, and Yan Zhou, and Feng Tian, and Yuan Ji, and Xin Cheng, and Guoyu Pan, and Yi-Tao Ding, and Lijian Hui
Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.

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.

UI MeSH Term Description Entries
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000418 Albumins Water-soluble proteins found in egg whites, blood, lymph, and other tissues and fluids. They coagulate upon heating. Albumin
D000641 Ammonia A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as AMMONIUM HYDROXIDE.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001663 Bilirubin A bile pigment that is a degradation product of HEME. Bilirubin IX alpha,Bilirubin, (15E)-Isomer,Bilirubin, (4E)-Isomer,Bilirubin, (4E,15E)-Isomer,Bilirubin, Calcium Salt,Bilirubin, Disodium Salt,Bilirubin, Monosodium Salt,Calcium Bilirubinate,Hematoidin,delta-Bilirubin,Bilirubinate, Calcium,Calcium Salt Bilirubin,Disodium Salt Bilirubin,Monosodium Salt Bilirubin,Salt Bilirubin, Calcium,delta Bilirubin
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D017114 Liver Failure, Acute A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C. Acute Hepatic Failure,Fulminant Hepatic Failure,Fulminating Hepatic Failure,Hepatic Failure, Fulminant,Liver Failure, Fulminant,Acute Liver Failure,Fulminating Liver Failure,Hepatic Failure, Acute,Failure, Acute Hepatic,Failure, Acute Liver,Fulminant Hepatic Failures,Fulminant Liver Failure,Fulminant Liver Failures,Fulminating Hepatic Failures,Fulminating Liver Failures,Hepatic Failure, Fulminating,Liver Failure, Fulminating
D019164 Liver, Artificial Devices for simulating the activities of the liver. They often consist of a hybrid between both biological and artificial materials. Artificial Liver,Bioartificial Liver,Artificial Livers,Bioartificial Livers,Liver, Bioartificial,Livers, Artificial,Livers, Bioartificial
D022781 Hepatocytes The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules. Hepatic Cells,Cell, Hepatic,Cells, Hepatic,Hepatic Cell,Hepatocyte

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