Large-scale Generation of Functional and Transplantable Hepatocytes and Cholangiocytes from Human Endoderm Stem Cells

doi:https://doi.org/10.1016/j.celrep.2020.108455

	Large-scale Generation of Functional and Transplantable Hepatocytes and Cholangiocytes from Human Endoderm Stem Cells
	Feng, Sisi 1; Wu, Jiaying 1; Qiu, Wei-Lin 2,3; Yang, Li 2,4; Deng, Xiaogang 1; Zhou, Ying 1; Chen, Yabin5 ; Li, Xiao 1; Yu, Lei 6; Li, Hongsheng 1; Xu, Zi-Ran 2,3; Xiao, Yini 1; Ren, Xiongzhao 1; Zhang, Ludi 1; Wang, Chenhua 1; Sun, Zhen5 ; Wang, Jinglin 7; Ding, Xiaoyan 1; Chen, Yuelei 1; Gadue, Paul 8,9; Pan, Guoyu 10; Ogawa, Mina 11,12; Ogawa, Shinichiro 11,12; Na, Jie 13; Zhang, Peilin 14; Hui, Lijian 1; Yin, Hao 15; Chen, Luonan5,16,17 ; Xu, Cheng-Ran 2; Cheng, Xin 1
	2020-12
发表期刊	CELL REPORTS
ISSN	2211-1247
卷号	33 期号:10
发表状态	已发表
DOI	https://doi.org/10.1016/j.celrep.2020.108455
摘要	The ever-increasing therapeutic and pharmaceutical demand for liver cells calls for systems that enable mass production of hepatic cells. Here we describe a large-scale suspension system that uses human endoderm stem cells (hEnSCs) as precursors to generate functional and transplantable hepatocytes (E-heps) or cholangiocytes (E-chos). hEnSC-derived hepatic populations are characterized by single-cell transcriptomic analyses and compared with hESC-derived counterparts, in-vitro-maintained or -expanded primary hepatocytes and adult cells, which reveals that hepatic differentiation of hEnSCs recapitulates in vivo development and that the heterogeneities of the resultant populations can be manipulated by regulating the EGF and MAPK signaling pathways. Functional assessments demonstrate that E-heps and E-chos possess properties comparable with adult counterparts and that, when transplanted intraperitoneally, encapsulated E-heps were able to rescue rats with acute liver failure. Our study lays the foundation for cell-based therapeutic agents and in vitro applications for liver diseases.
收录类别	SCI ; SCIE
语种	英语
资助项目	National Key R&D Program of China[2017YFA0102702][2017YFA0504501] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA16020203] ; National Natural Science Foundation of China[31771061] ; Scientific Instrument Developing Project of the Chinese Academy of Sciences[YJKYYQ20170042] ; Science and Technology Commission of Shanghai Municipality[15JC1400201] ; National Key Research and Development Program of China[2019YFA0801500] ; National Basic Research Program of China (973 Program)[2015CB942800]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000596872600009
出版者	CELL PRESS
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/124597
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_陈洛南组生命科学与技术学院_硕士生生命科学与技术学院_博士生
通讯作者	Yin, Hao; Chen, Luonan; Xu, Cheng-Ran; Cheng, Xin
作者单位	1.Chinese Acad Sci, Univ Chinese Acad Sci, State Key Lab Cell Biol, CAS Ctr Excellence Mol Cell Sci,Inst Biochem & Ce, Shanghai 200031, Peoples R China 2.Peking Univ, Coll Life Sci, Peking Tsinghua Ctr Life Sci, Minist Educ,Key Lab Cell Proliferat & Differentia, Beijing 10087, Peoples R China 3.Peking Univ, PKU Tsinghua NIBS Grad Program, Beijing 100871, Peoples R China 4.Peking Univ, Acad Adv Interdisciplinary Studies, Beijing 100871, Peoples R China 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China 6.Fudan Univ, Zhongshan Hosp, Liver Canc Inst,Minist Educ, Key Lab Carcinogenesis & Canc Invas,Dept Liver Su, Shanghai 200032, Peoples R China 7.Nanjing Univ, Dept Hepatobiliary Surg, Affiliated Drum Tower Hosp, Med Sch, Nanjing 21008, Peoples R China 8.Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA 9.Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA 10.Chinese Acad Sci, Ctr Drug Safety Evaluat & Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 11.Univ Hlth Network, McEwen Ctr Regenerat Med, Toronto, ON, Canada 12.Univ Hlth Network, Toronto Gen Res Inst, Toronto, ON, Canada 13.Tsinghua Univ, Ctr Stem Cell Biol & Regenerat Med, Sch Med, Beijing 100084, Peoples R China 14.Second Mil Med Univ, Eastern Hepatobiliary Surg Inst Hosp, Int Cooperat Lab Signal Transduct, Shanghai 200438, Peoples R China 15.Second Mil Med Univ, Shanghai Changzheng Hosp, Organ Transplant Ctr, Shanghai 200003, Peoples R China 16.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Inst Biochem & Cell Biol, Key Lab Syst Biol,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China 17.Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming 650223, Yunnan, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Feng, Sisi,Wu, Jiaying,Qiu, Wei-Lin,et al. Large-scale Generation of Functional and Transplantable Hepatocytes and Cholangiocytes from Human Endoderm Stem Cells[J]. CELL REPORTS,2020,33(10).
APA	Feng, Sisi.,Wu, Jiaying.,Qiu, Wei-Lin.,Yang, Li.,Deng, Xiaogang.,...&Cheng, Xin.(2020).Large-scale Generation of Functional and Transplantable Hepatocytes and Cholangiocytes from Human Endoderm Stem Cells.CELL REPORTS,33(10).
MLA	Feng, Sisi,et al."Large-scale Generation of Functional and Transplantable Hepatocytes and Cholangiocytes from Human Endoderm Stem Cells".CELL REPORTS 33.10(2020).