Microfluidic Organ-on-a-Chip Models of Human Intestine

Abstract

Microfluidic organ-on-a-chip models of human intestine have been developed and used to study intestinal physiology and pathophysiology. In this article, we review this field and describe how microfluidic Intestine Chips offer new capabilities not possible with conventional culture systems or organoid cultures, including the ability to analyze contributions of individual cellular, chemical, and physical control parameters one-at-a-time; to coculture human intestinal cells with commensal microbiome for extended times; and to create human-relevant disease models. We also discuss potential future applications of human Intestine Chips, including how they might be used for drug development and personalized medicine.

Keywords: 3D, 3-dimensional; ECM, extracellular matrix; Gut-on-a-Chip; IBD, inflammatory bowel disease; Intestine-on-a-Chip; Microfluidic; Organs-on-Chips; PD, pharmacodynamics; PDMS, polydimethylsiloxane; PK, pharmacokinetics.

Figure 1

The mechanically active human Gut Chip. (A) Human villus intestinal epithelium and vascular endothelium are lined on opposite sides of a flexible porous membrane under fluid flows and peristalsis-like strains. A zoom-in schematic shows the intestinal microenvironment undergoing complex crosstalk between commensal gut microbiome, bacterial pathogens, and immune cells in parenchymal and vascular channels, respectively. Figure modified with permission from Reference 75. (B) Villus morphogenesis of human Caco-2 intestinal epithelium in the Gut Chip under physiologically controlled motions and flow. Figure modified with permission from References 17 and 42. (C) An overlaid image of the coculture of green fluorescent protein–labeled Escherichia coli and microengineered villi in the Gut Chip. Bars = 50 μm.