Human vascularized bile duct-on-a chip: a multi-cellular micro-physiological system for studying cholestatic liver disease

doi:10.1088/1758-5090/ad0261

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	Human vascularized bile duct-on-a chip: a multi-cellular micro-physiological system for studying cholestatic liver disease
	Du, Yu1,2,3,4 ; de Jong, Iris E. M.1,4; Gupta, Kapish 1,4; Waisbourd-Zinman, Orit 5,6; Har-Zahav, Adi 5,6; Soroka, Carol J.7; Boyer, James L.7; Llewellyn, Jessica 1,4; Liu, Chengyang 8; Naji, Ali 8; Polacheck, William J.9,10; Wells, Rebecca G.1,4,11,12
通讯作者	Wells, Rebecca G.(rgwells@pennmedicine.upenn.edu)
发表期刊	BIOFABRICATION
	2024
卷号	16 期号:1 页码:13
ISSN	1758-5082
摘要	Exploring the pathogenesis of and developing therapies for cholestatic liver diseases such as primary sclerosing cholangitis (PSC) remains challenging, partly due to a paucity of in vitro models that capture the complex environments contributing to disease progression and partly due to difficulty in obtaining cholangiocytes. Here we report the development of a human vascularized bile duct-on-a-chip (VBDOC) that uses cholangiocyte organoids derived from normal bile duct tissue and human vascular endothelial cells to model bile ducts and blood vessels structurally and functionally in three dimensions. Cholangiocytes in the duct polarized, formed mature tight junctions and had permeability properties comparable to those measured in ex vivo systems. The flow of blood and bile was modeled by perfusion of the cell-lined channels, and cholangiocytes and endothelial cells displayed differential responses to flow. We also showed that the device can be constructed with biliary organoids from cells isolated from both bile duct tissue and the bile of PSC patients. Cholangiocytes in the duct became more inflammatory under the stimulation of IL-17A, which induced peripheral blood mononuclear cells and differentiated Th17 cells to transmigrate across the vascular channel. In sum, this human VBDOC recapitulated the vascular-biliary interface structurally and functionally and represents a novel multicellular platform to study inflammatory and fibrotic cholestatic liver diseases.
关键词	microfluidic device cholangiopathy tissue engineering organ-on-a-chip primary sclerosing cholangitis
DOI	10.1088/1758-5090/ad0261
收录类别	SCI
语种	英语
WOS记录号	WOS:001087075000001
关键词[WOS]	PRIMARY SCLEROSING CHOLANGITIS ; ORGANOIDS ; CELLS ; DIFFERENTIATION ; CULTURE
WOS研究方向	Engineering ; Materials Science
WOS类目	Engineering, Biomedical ; Materials Science, Biomaterials
资助项目	We gratefully acknowledge the assistance of the following core facilities and individuals at the University of Pennsylvania: the Perelman School of Medicine Cell and Developmental Biology Microscopy Core and Andrea Stout, the Human Immunology Core, and the[NIH P30 DK050306] ; NIDDK Center for Molecular Studies in Digestive and Liver Diseases Molecular Pathology and Imaging Core
项目资助者	We gratefully acknowledge the assistance of the following core facilities and individuals at the University of Pennsylvania: the Perelman School of Medicine Cell and Developmental Biology Microscopy Core and Andrea Stout, the Human Immunology Core, and the ; NIDDK Center for Molecular Studies in Digestive and Liver Diseases Molecular Pathology and Imaging Core
引用统计	被引频次：2[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://dspace.imech.ac.cn/handle/311007/93280
专题	微重力重点实验室
通讯作者	Wells, Rebecca G.
作者单位	1.Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA 2.Chinese Acad Sci, Key Lab Micrograv, Ctr Biomech & Bioengn, Natl Micrograv Lab, Beijing 100190, Peoples R China 3.Chinese Acad Sci, Inst Mech, Beijing Key Lab Engn Construct & Mechanobiol, Beijing 100190, Peoples R China 4.Univ Penn, NSF Sci & Technol Ctr Engn MechanoBiol, Philadelphia, PA 19104 USA 5.Schneider Childrens Med Ctr Israel, Inst Gastroenterol Nutr & Liver Dis, Petah Tiqwa, Israel 6.Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel 7.Yale Univ, Sect Digest Dis& Liver Ctr, Dept Internal Med, Sch Med, New Haven, CT USA 8.Univ Penn, Dept Surg, Philadelphia, PA USA 9.Univ North Carolinaat Chapel Hill, Joint Dept Biomed Engn, Chapel Hill, NC USA 10.North Carolina State Univ, Chapel Hill, NC USA 11.Univ Penn, Sch Engn & Appl Sci, Dept Bioengn, Philadelphia, PA 19104 USA 12.Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA
推荐引用方式 GB/T 7714	Du, Yu,de Jong, Iris E. M.,Gupta, Kapish,et al. Human vascularized bile duct-on-a chip: a multi-cellular micro-physiological system for studying cholestatic liver disease[J]. BIOFABRICATION,2024,16,1,:13.
APA	Du, Yu.,de Jong, Iris E. M..,Gupta, Kapish.,Waisbourd-Zinman, Orit.,Har-Zahav, Adi.,...&Wells, Rebecca G..(2024).Human vascularized bile duct-on-a chip: a multi-cellular micro-physiological system for studying cholestatic liver disease.BIOFABRICATION,16(1),13.
MLA	Du, Yu,et al."Human vascularized bile duct-on-a chip: a multi-cellular micro-physiological system for studying cholestatic liver disease".BIOFABRICATION 16.1(2024):13.