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Mimicking liver sinusoidal structures and functions using a 3D-configured microfluidic chip
Du Y(杜宇); Li N(李宁); Yang H(杨浩); Luo CH(罗春花); Gong YX; Tong CF(佟春芳); Gao YX(高宇新); Lv SQ(吕守芹); Long M(龙勉); Long, M (reprint author), Chinese Acad Sci, Key Lab Micrograv, Natl Micrograv Lab, Ctr Biomech & Bioengn, Beijing 100190, Peoples R China.; Long, M (reprint author), Chinese Acad Sci, Beijing Key Lab Engn Construct & Mech, Inst Mech, Beijing 100190, Peoples R China.; Long, M (reprint author), Univ Chinese Acad Sci, Sch Engn Sci, Beijing 100049, Peoples R China.
Source PublicationLAB ON A CHIP
2017
Volume17Issue:5Pages:782-794
ISSN1473-0197
AbstractPhysiologically four major types of hepatic cells - the liver sinusoidal endothelial cells Kupffer cells hepatic stellate cells and hepatocytes - reside inside liver sinusoids and interact with flowing peripheral cells under blood flow. It is hard to mimic an in vivo liver sinusoid due to its complex multiple cell-cell interactions spatiotemporal construction and mechanical microenvironment. Here we developed an in vitro liver sinusoid chip by integrating the four types of primary murine hepatic cells into two adjacent fluid channels separated by a porous permeable membrane replicating liver's key structures and configurations. Each type of cells was identified with its respective markers and the assembled chip presented the liver-specific unique morphology of fenestration. The flow field in the liver chip was quantitatively analyzed by computational fluid dynamics simulations and particle tracking visualization tests. Intriguingly co-culture and shear flow enhance albumin secretion independently or cooperatively while shear flow alone enhances HGF production and CYP450 metabolism. Under lipopolysaccharide (LPS) stimulations the hepatic cell co-culture facilitated neutrophil recruitment in the liver chip. Thus this 3D-configured in vitro liver chip integrates the two key factors of shear flow and the four types of primary hepatic cells to replicate key structures hepatic functions and primary immune responses and provides a new in vitro model to investigate the short-duration hepatic cellular interactions under a microenvironment mimicking the physiology of a liver.
DOI10.1039/c6lc01374k
Indexed BySCI
Language英语
WOS IDWOS:000395893500003
WOS KeywordON-A-CHIP ; ENDOTHELIAL-CELLS ; IN-VITRO ; DIFFERENTIAL REGULATION ; METABOLIC-ACTIVITY ; STEM-CELLS ; RAT-LIVER ; FLOW ; HEPATOCYTES ; MORPHOLOGY
WOS Research AreaBiochemistry & Molecular Biology ; Chemistry ; Science & Technology - Other Topics
WOS SubjectBiochemical Research Methods ; Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology
Funding OrganizationNational Natural Science Foundation of China(31230027 ; CAS Strategic Priority Research Program(XDA01030604 ; 91642203 ; XDB22040101) ; 31661143044 ; 31110103918)
DepartmentNML分子-细胞生物力学与空间生命科学
Classification一类
Ranking1
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Cited Times:30[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://dspace.imech.ac.cn/handle/311007/60599
Collection国家微重力实验室
Corresponding AuthorLong, M (reprint author), Chinese Acad Sci, Key Lab Micrograv, Natl Micrograv Lab, Ctr Biomech & Bioengn, Beijing 100190, Peoples R China.; Long, M (reprint author), Chinese Acad Sci, Beijing Key Lab Engn Construct & Mech, Inst Mech, Beijing 100190, Peoples R China.; Long, M (reprint author), Univ Chinese Acad Sci, Sch Engn Sci, Beijing 100049, Peoples R China.
Recommended Citation
GB/T 7714
Du Y,Li N,Yang H,et al. Mimicking liver sinusoidal structures and functions using a 3D-configured microfluidic chip[J]. LAB ON A CHIP,2017,17(5):782-794.
APA 杜宇.,李宁.,杨浩.,罗春花.,Gong YX.,...&Long, M .(2017).Mimicking liver sinusoidal structures and functions using a 3D-configured microfluidic chip.LAB ON A CHIP,17(5),782-794.
MLA 杜宇,et al."Mimicking liver sinusoidal structures and functions using a 3D-configured microfluidic chip".LAB ON A CHIP 17.5(2017):782-794.
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