Human vascularized bile duct-on-a chip: a multi-cellular micro-physiological system for studying cholestatic liver disease
文献类型：期刊论文
| 作者 | Du, Yu9,10,11,12 ; de Jong, Iris E. M.9,12; Gupta, Kapish9,12; Waisbourd-Zinman, Orit7,8; Har-Zahav, Adi7,8; Soroka, Carol J.6; Boyer, James L.6; Llewellyn, Jessica9,12; Liu, Chengyang5; Naji, Ali5
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| 刊名 | BIOFABRICATION
 |
| 出版日期 | 2024 |
| 卷号 | 16期号:1页码:13 |
| ISSN号 | 1758-5082 |
| 关键词 | microfluidic device cholangiopathy tissue engineering organ-on-a-chip primary sclerosing cholangitis |
| DOI | 10.1088/1758-5090/ad0261 |
| 通讯作者 | Wells, Rebecca G.(rgwells@pennmedicine.upenn.edu) |
| 英文摘要 | 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. |
| WOS关键词 | PRIMARY SCLEROSING CHOLANGITIS ; ORGANOIDS ; CELLS ; DIFFERENTIATION ; CULTURE |
| 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 |
| WOS研究方向 | Engineering ; Materials Science |
| 语种 | 英语 |
| WOS记录号 | WOS:001087075000001 |
| 资助机构 | 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 |
| 源URL | [http://dspace.imech.ac.cn/handle/311007/93279]  |
| 专题 | 力学研究所_国家微重力实验室 |
| 通讯作者 | Wells, Rebecca G. |
| 作者单位 | 1.Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA 2.Univ Penn, Sch Engn & Appl Sci, Dept Bioengn, Philadelphia, PA 19104 USA 3.North Carolina State Univ, Chapel Hill, NC USA 4.Univ North Carolinaat Chapel Hill, Joint Dept Biomed Engn, Chapel Hill, NC USA 5.Univ Penn, Dept Surg, Philadelphia, PA USA 6.Yale Univ, Sect Digest Dis& Liver Ctr, Dept Internal Med, Sch Med, New Haven, CT USA 7.Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel 8.Schneider Childrens Med Ctr Israel, Inst Gastroenterol Nutr & Liver Dis, Petah Tiqwa, Israel 9.Univ Penn, NSF Sci & Technol Ctr Engn MechanoBiol, Philadelphia, PA 19104 USA 10.Chinese Acad Sci, Inst Mech, Beijing Key Lab Engn Construct & Mechanobiol, Beijing 100190, Peoples R China |
| 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. |
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来源：力学研究所
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