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

doi:10.1038/cr.2016.6

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	Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes
	Shi, Xiao-Lei 3; Gao, Yimeng 1; Yan, Yupeng 1; Ma, Hucheng 3; Sun, Lulu 1; Huang, Pengyu 1,2; Ni, Xuan 4; Zhang, Ludi 1; Zhao, Xin 3; Ren, Haozhen 3
刊名	CELL RESEARCH
	2016-02
卷号	26 期号:2 页码:206-216
关键词	acute liver failure functional hepatocytes bioartificial liver
ISSN号	1001-0602
DOI	10.1038/cr.2016.6
文献子类	Article
英文摘要	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.
资助项目	"Strategic Priority Research Program" of CAS[XDA01030601] ; "Strategic Priority Research Program" of CAS[XDA01030602] ; National Natural Science Foundation of China (NSFC)[31225016] ; National Natural Science Foundation of China (NSFC)[91319307] ; National Natural Science Foundation of China (NSFC)[81471948] ; Ministry of Science and Technology of China (MOST)[2013CB967103] ; Ministry of Science and Technology of China (MOST)[2012CB945001] ; Science and Technology Commission of Shanghai Municipality (STCSM)[14XD1404200] ; Science and Technology Commission of Shanghai Municipality (STCSM)[15JC1400200] ; NSFC[81170418] ; NSFC[81302836] ; Natural Science Foundation of Jiangsu Province[BK20131084] ; MOST[2013AA032202] ; Fudan Foundation[2013ZSQN28] ; STCSM[14YF1406900]
WOS关键词	CELL-DERIVED HEPATOCYTES ; IN-VITRO EVALUATION ; SUPPORT-SYSTEM ; ASSIST DEVICE ; CONTROLLED-TRIAL ; BIOREACTOR ; TRANSPLANTATION ; PRESERVATION ; SCAFFOLDS ; REVERSAL
WOS研究方向	Cell Biology
语种	英语
CSCD记录号	CSCD:5651155
出版者	INST BIOCHEMISTRY & CELL BIOLOGY
WOS记录号	WOS:000372062300008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276155]
专题	药物安全性评价中心
通讯作者	Pan, Guoyu; Ding, Yi-Tao; Hui, Lijian
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China; 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 3.Nanjing Univ, Sch Med, Dept Hepatobiliary Surg, Affiliated Drum Tower Hosp, Nanjing 210008, Jiangsu, 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
推荐引用方式 GB/T 7714	Shi, Xiao-Lei,Gao, Yimeng,Yan, Yupeng,et al. Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes[J]. CELL RESEARCH,2016,26(2):206-216.
APA	Shi, Xiao-Lei.,Gao, Yimeng.,Yan, Yupeng.,Ma, Hucheng.,Sun, Lulu.,...&Hui, Lijian.(2016).Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes.CELL RESEARCH,26(2),206-216.
MLA	Shi, Xiao-Lei,et al."Improved survival of porcine acute liver failure by a bioartificial liver device implanted with induced human functional hepatocytes".CELL RESEARCH 26.2(2016):206-216.