Shin Woojung, Kim Hyun Jung
Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, United States.
Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, United States.
Methods Cell Biol. 2018;146:135-148. doi: 10.1016/bs.mcb.2018.05.006. Epub 2018 Jun 25.
The gut-on-a-chip is a microengineered in vitro model of the living human intestine that reconstitutes the lumen-capillary tissue interface. Intestinal epithelial Caco-2 cells cultured on the extracellular matrix-coated porous membrane in a gut-on-a-chip undergo three-dimensional villus morphogenesis and physiological cytodifferentiation. The gut-on-a-chip closely recapitulates biomechanical and functional characteristics under peristalsis-like cyclic movements and trickling flow, which enables to co-culture gut microbiome with villus epithelium from days to weeks. Host-gut microbiome ecosystem emulated in the gut-on-a-chip allows the pathomimetic modeling of human intestinal diseases such as gut inflammation and bacterial overgrowth. Here, we describe a protocol for microfabrication of a gut-on-a-chip device, reconstitution of intestinal microenvironment, recreation of host-gut microbiome intercellular interactions, and demonstration of the pathophysiology of representative human intestinal diseases associated with the gut microbiome. The modeling of intestinal disease pathophysiology on-chip can potentiate the development of patient-specific disease models that can validate the efficacy and safety of novel therapeutic interventions.
肠道芯片是一种对活的人体肠道进行微工程处理的体外模型，它重建了管腔-毛细血管组织界面。在肠道芯片中，在细胞外基质包被的多孔膜上培养的肠道上皮Caco-2细胞会经历三维绒毛形态发生和生理细胞分化。肠道芯片在类似蠕动的循环运动和滴流作用下，能紧密重现生物力学和功能特性，这使得肠道微生物群能够与绒毛上皮共同培养数天至数周。在肠道芯片中模拟的宿主-肠道微生物群生态系统允许对诸如肠道炎症和细菌过度生长等人类肠道疾病进行病理模拟建模。在此，我们描述了一种用于肠道芯片装置微制造、肠道微环境重建、宿主-肠道微生物群细胞间相互作用重现以及与肠道微生物群相关的代表性人类肠道疾病病理生理学演示的方案。芯片上肠道疾病病理生理学的建模可以促进患者特异性疾病模型的开发，这些模型可以验证新型治疗干预措施的疗效和安全性。
