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In situ differentiation and generation of functional liver organoids from human iPSCs in a 3D perfusable chip system

文献类型：期刊论文

作者Tao, Tingting1,4; Wang, Yaqing1,4; Wang, Hui1,4; Deng, Pengwei1,4; Chen, Wenwen1,4; Guo, Yaqiong1,4; Qin, Jianhua1,2,3,4
刊名LAB ON A CHIP
出版日期2018-12-07
卷号18期号:23页码:3606-3616
ISSN号1473-0197
DOI10.1039/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
资助项目Strategic Priority Research Program of the Chinese Academy of Sciences[XDA16020900] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDP0305] ; National Key R&D Program of China[2017YFB0405400] ; International Science & Technology Cooperation Program of China[2015DFA00740] ; Key Program of the Chinese Academy of Sciences[KFZD-SW-213] ; National Natural Science Foundation of China[91543121] ; National Natural Science Foundation of China[31671038] ; National Natural Science Foundation of China[81573394] ; National Natural Science Foundation of China[31600784] ; Innovation Program of Science and Research from the DICP, CAS[DICP TMSR201601]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry ; Science & Technology - Other Topics
语种英语
WOS记录号WOS:000450737200004
出版者ROYAL SOC CHEMISTRY
资助机构Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Key R&D Program of China ; National Key R&D Program of China ; International Science & Technology Cooperation Program of China ; International Science & Technology Cooperation Program of China ; Key Program of the Chinese Academy of Sciences ; Key Program of the Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Innovation Program of Science and Research from the DICP, CAS ; Innovation Program of Science and Research from the DICP, CAS ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Key R&D Program of China ; National Key R&D Program of China ; International Science & Technology Cooperation Program of China ; International Science & Technology Cooperation Program of China ; Key Program of the Chinese Academy of Sciences ; Key Program of the Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Innovation Program of Science and Research from the DICP, CAS ; Innovation Program of Science and Research from the DICP, CAS ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Key R&D Program of China ; National Key R&D Program of China ; International Science & Technology Cooperation Program of China ; International Science & Technology Cooperation Program of China ; Key Program of the Chinese Academy of Sciences ; Key Program of the Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Innovation Program of Science and Research from the DICP, CAS ; Innovation Program of Science and Research from the DICP, CAS ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Key R&D Program of China ; National Key R&D Program of China ; International Science & Technology Cooperation Program of China ; International Science & Technology Cooperation Program of China ; Key Program of the Chinese Academy of Sciences ; Key Program of the Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Innovation Program of Science and Research from the DICP, CAS ; Innovation Program of Science and Research from the DICP, CAS
源URL[http://cas-ir.dicp.ac.cn/handle/321008/166526]  
专题大连化学物理研究所_中国科学院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		 Tao, Tingting,Wang, Yaqing,Wang, Hui,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 Tao, Tingting.,Wang, Yaqing.,Wang, Hui.,Deng, Pengwei.,Chen, Wenwen.,...&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 Tao, Tingting,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.

入库方式： OAI收割

来源：大连化学物理研究所

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