文献类型：期刊文献

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

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

作者：Xiao-Lei Shi[1];Yimeng Gao[2];YupengYan[2];HuchengMa[1];Lulu Sun[2];Pengyu Huang[2,3];Xuan Ni[4];Ludi Zhang[2];Xin Zhao[1];Haozhen Ren[1];Dan Hu[5];Yan Zhou[5];Feng Tian[6];Yuan Ji[6];Xin Cheng[2];Guoyu Pan[4];Yi-Tao Ding[1];LijianHui[2,3]

机构：[1]Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China;[2]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;[3]School of Life Science and Technology, Shang- haiTech University, Shanghai, China;[4]Center for Drug Safety Evahtation and Research, Shanghai Institute of Materia Mediea, Chinese Academy of Sciences, Shanghai, China;[5]State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, Shanghai, China;[6]Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China

年份：2016

卷号：26

期号：2

起止页码：206

中文期刊名：Cell Research

外文期刊名：细胞研究（英文版）

收录：CSTPCD;;Scopus;CSCD:【CSCD2015_2016】；PubMed;

语种：英文

中文关键词：acute liver failure; functional hepatocytes; bioartificial liver

外文关键词：肝功能衰竭;人肝细胞;生物人工肝;急性;猪;植入;诱导;装置

摘要：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.