Physiological oxygen tension reduces hepatocyte dedifferentiation in in vitro culture

doi:10.1038/s41598-017-06433-3

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	Physiological oxygen tension reduces hepatocyte dedifferentiation in in vitro culture
	Guo, Ren 3,4; Xu, Xinxiu 3; Lu, Yuting 1,3; Xie, Xin1,2,3
刊名	SCIENTIFIC REPORTS
	2017-07-19
卷号	7
ISSN号	2045-2322
DOI	10.1038/s41598-017-06433-3
文献子类	Article
英文摘要	Primary hepatocytes cultured in vitro are a powerful tool to study the functions of hepatocytes and to evaluate the metabolism and toxicity of new drugs. However, in vitro culture of hepatocytes has proven to be very difficult. Ordinary culture conditions lead to dedifferentiation of hepatocytes, resulting in rapid change in cell morphology and significant reduction in specific cell functions. In the current study, we show that hepatocyte dedifferentiation is a rapid process under 21% O-2 conditions. Hepatocytes cultured in 21% O-2 undergo epithelial-to-mesenchymal transition (EMT), obtain fibroblast-like morphology, and show decreased hepatic functions. In contrast, 5% O-2 is very effective in maintaining the epithelial morphology and many functions of the primary hepatocytes cultured in vitro for up to five days. These functions include albumin production, glycogen storage, LDL-uptake and CYP450-mediated drug metabolism. Furthermore, we find that 5% O-2 can relieve the production of reactive oxygen species (ROS) and decrease the level of DNA damage in primary cultured hepatocytes. In addition, we also show that blocking the ERK and GSK-3 beta pathways can inhibit the dedifferentiation of hepatocytes to a certain extent. Lowering the oxygen tension in cell culture is easily achievable, we believe it could be combined with other methods, such as the use of small molecule cocktails and 3D culture, to maintain proliferation and functions of primary hepatocytes in vitro.
资助项目	Ministry of Science and Technology of China[2015CB964503] ; Chinese Academy of Sciences[XDA01040301] ; National Natural Science Foundation of China[81425024] ; National Natural Science Foundation of China[31371511] ; National Natural Science Foundation of China[81472862] ; National Natural Science Foundation of China[31501189] ; Shanghai Science and Technology Committee[14ZR1409500] ; Shanghai Science and Technology Committee[15YF1402400]
WOS关键词	EMBRYONIC STEM-CELLS ; EPITHELIAL-MESENCHYMAL TRANSITION ; HUMAN INDUCED PLURIPOTENT ; LIVER DEVELOPMENT ; ENZYME-INDUCTION ; SMALL MOLECULES ; HYPOXIA ; DIFFERENTIATION ; REGENERATION ; HEPATOTOXICITY
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000405895400020
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272563]
专题	国家新药筛选中心
通讯作者	Xie, Xin
作者单位	1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 2.Tongji Univ, Shanghai Key Lab Signaling & Dis Res, Lab Receptor Based Biomed, Sch Life Sci & Technol, Shanghai 200092, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 4.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China;
推荐引用方式 GB/T 7714	Guo, Ren,Xu, Xinxiu,Lu, Yuting,et al. Physiological oxygen tension reduces hepatocyte dedifferentiation in in vitro culture[J]. SCIENTIFIC REPORTS,2017,7.
APA	Guo, Ren,Xu, Xinxiu,Lu, Yuting,&Xie, Xin.(2017).Physiological oxygen tension reduces hepatocyte dedifferentiation in in vitro culture.SCIENTIFIC REPORTS,7.
MLA	Guo, Ren,et al."Physiological oxygen tension reduces hepatocyte dedifferentiation in in vitro culture".SCIENTIFIC REPORTS 7(2017).