Bile Duct-on-a-Chip

Abstract

Cholangiopathies affect the biliary tree via various pathophysiological mechanisms. Research on biliary physiology and pathology, however, is hampered by a lack of physiologically relevant in vitro models. Conventional models, such as two-dimensional (2D) monolayers and organoids, fail to replicate the structural organization of the bile duct, and both the size of the duct and position of cells are difficult to manipulate in a controllable way. Here, we describe a bile duct-on-a-chip (BDOC) that phenocopies the open-ended tubular architecture of the bile duct in three dimensions which, when seeded with either a cholangiocyte cell line or primary cells, demonstrates barrier function similar to bile ducts in vivo. This device represents an in vitro platform to study the pathophysiology of the bile duct using cholangiocytes from a variety of sources.

Keywords: 3D cell culture; Bile duct epithelium; Biliary model; Cholangiopathy; Microfluidics; Organ-on-chip; Organotypic model.

Fig. 1.

Flow chart showing fabrication process.

Fig. 2.

A. Top view of a bile duct-on-a-chip. B. Representative immunofluorescent image of the cholangiocyte tube in the device, stained with F-actin (red) and nuclei (DAPI, blue). C. Representative bright field image of the cholangiocytes lining channel. D. Fluorescent FITC-dextran (70, 10, 4 kDa) in the channel, imaged after 15 min. Scale bar, 100 μm (B, C), 200 μm (D). Figure adapted from Du Y, Khandekar G, Llewellyn J, Polacheck W, Chen CS, Wells RG. A Bile Duct-on-a-Chip With Organ-Level Functions. Hepatology 2020;71:1350–1363. under the terms of the Creative Commons Attribution Non-Commercial License CC BY-NC.