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	In situ differentiation and generation of functional liver organoids from human ipscs in a 3d perfusable chip system
	Wang, Yaqing1,4; Wang, Hui1,4; Deng, Pengwei1,4; Chen, Wenwen1,4; Guo, Yaqiong1,4; Tao, Tingting1,4; Qin, Jianhua1,2,3,4
刊名	Lab on a chip
	2018-12-07
卷号	18期号:23页码:3606-3616
ISSN号	1473-0197
DOI	10.1039/c8lc00869h
通讯作者	Qin, jianhua(jhqin@dicp.ac.cn)
英文摘要	Liver organoids derived from human pluripotent stem cells (pscs) represent a new type of in vitro liver model for understanding organ development, disease mechanism and drug testing. however, engineering liver organoids with favorable functions in a controlled cellular microenvironment remains challenging. in this work, we present a new strategy for engineering liver organoids derived from human induced pscs (hipscs) in a 3d perfusable chip system by combining stem cell biology with microengineering technology. this approach enabled formation of hipsc-based embryoid bodies (ebs), in situ hepatic differentiation, long-term 3d culture and generation of liver organoids in a perfusable micropillar chip. the generated liver organoids exhibited favorable growth and differentiation of hepatocytes and cholangiocytes, recapitulating the key features of human liver formation with cellular heterogeneity. the liver organoids in perfused cultures displayed improved cell viability and higher expression of endodermal genes (sox17 and foxa2) and mature hepatic genes (alb and cyp3a4) under perfused culture conditions. in addition, the liver organoids showed a marked enhancement of hepatic-specific functions, including albumin and urea production and metabolic capabilities, indicating the role of mechanical fluid flow in promoting the functions of the liver organoids. moreover, the liver organoids exhibited hepatotoxic response after exposure to acetaminophen (apap) in a dose- and time-dependent manner. the established liver organoid-on-a-chip system may provide a promising platform for engineering stem cell-based organoids with applications in regenerative medicine, disease modeling and drug testing.
WOS关键词	PLURIPOTENT STEM-CELLS ; ON-A-CHIP ; MODEL ; ORGANOGENESIS ; PLATFORM
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry ; Science & Technology - Other Topics
WOS类目	Biochemical Research Methods ; Chemistry, Multidisciplinary ; Chemistry, Analytical ; Nanoscience & Nanotechnology
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000450737200004
内容类型	期刊论文
URI标识	http://www.corc.org.cn/handle/1471x/2373023
专题	大连化学物理研究所
通讯作者	Qin, Jianhua
作者单位	1.Chinese Acad Sci, Dalian Inst Chem Phys, Div Biotechnol, CAS Key Lab Separat Sci Analyt Chem, 457 Zhongshan Rd, Dalian 116023, Peoples R China 2.Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing, Peoples R China 3.Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Shanghai, Peoples R China 4.Univ Chinese Acad Sci, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Wang, Yaqing,Wang, Hui,Deng, Pengwei,et al. In situ differentiation and generation of functional liver organoids from human ipscs in a 3d perfusable chip system[J]. Lab on a chip,2018,18(23):3606-3616.
APA	Wang, Yaqing.,Wang, Hui.,Deng, Pengwei.,Chen, Wenwen.,Guo, Yaqiong.,...&Qin, Jianhua.(2018).In situ differentiation and generation of functional liver organoids from human ipscs in a 3d perfusable chip system.Lab on a chip,18(23),3606-3616.
MLA	Wang, Yaqing,et al."In situ differentiation and generation of functional liver organoids from human ipscs in a 3d perfusable chip system".Lab on a chip 18.23(2018):3606-3616.

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