Du Yu, Polacheck William J, Wells Rebecca G
Division of Gastroenterology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Center for Engineering MechanoBiology, The University of Pennsylvania, Philadelphia, PA, USA.
Methods Mol Biol. 2022;2373:57-68. doi: 10.1007/978-1-0716-1693-2_4.
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.
胆管病通过多种病理生理机制影响胆管树。然而,由于缺乏生理相关的体外模型,胆管生理和病理研究受到阻碍。传统模型,如二维(2D)单层细胞和类器官,无法复制胆管的结构组织,并且胆管的大小和细胞位置都难以以可控的方式进行操作。在这里,我们描述了一种胆管芯片(BDOC),它在三维空间中模拟了胆管的开放式管状结构,当接种胆管上皮细胞系或原代细胞时,表现出与体内胆管相似的屏障功能。该装置代表了一个体外平台,可用于使用来自各种来源的胆管上皮细胞研究胆管的病理生理学。