Physiological oxygen tension reduces hepatocyte dedifferentiation in in vitro culture

doi:10.1038/s41598-017-06433-3

	Physiological oxygen tension reduces hepatocyte dedifferentiation in in vitro culture
	Guo, Ren 1,2; Xu, Xinxiu 1; Lu, Yuting1,3 ; Xie, Xin1,3,4
	2017-07-19
发表期刊	SCIENTIFIC REPORTS
ISSN	2045-2322
卷号	7
发表状态	已发表
DOI	10.1038/s41598-017-06433-3
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.
收录类别	SCI
语种	英语
资助项目	Shanghai Science and Technology Committee[14ZR1409500] ; Shanghai Science and Technology Committee[15YF1402400]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000405895400020
出版者	NATURE PUBLISHING GROUP
WOS关键词	HUMAN INDUCED PLURIPOTENT ; EMBRYONIC STEM-CELLS ; LIVER DEVELOPMENT ; SMALL MOLECULES ; DIFFERENTIATION ; METABOLISM ; HEPATOTOXICITY ; REGENERATION ; MECHANISMS ; GENERATION
原始文献类型	Article
通讯作者	Xie, Xin
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/2893
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_谢欣组生命科学与技术学院_博士生
通讯作者	Xie, Xin
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 4.Tongji Univ, Shanghai Key Lab Signaling & Dis Res, Lab Receptor Based Biomed, Sch Life Sci & Technol, Shanghai 200092, 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	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).