文献类型：期刊文献

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

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

机构：[1]Nanjing Univ, Sch Med, Dept Hepatobiliary Surg, Affiliated Drum Tower Hosp, Nanjing 210008, Jiangsu, Peoples R China;[2]Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China;[3]ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China;[4]Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, Shanghai 200031, Peoples R China;[5]E China Univ Sci & Technol, Sch Bioengn, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[6]Fudan Univ, Dept Pathol, Zhongshan Hosp, Shanghai 200433, Peoples R China

年份：2016

卷号：26

期号：2

起止页码：206

外文期刊名：CELL RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000372062300008)】；

基金：We are thankful to Qi Zhou, Jianwu Dai, Guihai Wang and Yi Shen (Chinese Academy of Sciences (CAS), China) for suggestions and supports on the project, and David Hay (University of Edinburgh, UK) and Yunwen Zheng (University of Tsukuba, Japan) for critical reading of the manuscript. L Hui lab is supported by the "Strategic Priority Research Program" of CAS (XDA01030601), the National Natural Science Foundation of China (NSFC; 31225016, 91319307 and 81471948), the Ministry of Science and Technology of China (MOST; 2013CB967103 and 2012CB945001), and the Science and Technology Commission of Shanghai Municipality (STCSM; 14XD1404200 and 15JC1400200). Y-T Ding lab is supported by NSFC (81170418), the Natural Science Foundation of Jiangsu Province (BK20131084), and the "Strategic Priority Research Program" of CAS (XDA01030602). G Pan lab is supported by NSFC (81302836) and MOST (2013AA032202). Y Ji lab is supported by Fudan Foundation for Young Investigator (2013ZSQN28). P Huang lab is supported by STCSM (14YF1406900).

语种：英文

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

摘要：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 alpha-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.