Discussion

The intestinal epithelium represents a key interface between the external environment and the internal host milieu. In addition to facilitating per os compound absorption, barrier disruption and dysbiosis are characteristic of conditions such as inflammatory bowel disease (IBD) (1). While traditional 2D gut models, for example Caco-2 cells, may have utility in screening contexts, such systems omit much of the cellular complexity and mechanical cues found in vivo, contributing to drug attrition (2). Using organ-on-chip technology and the proprietary Human Emulation System (Emulate, Inc, Boston, MA), Caco-2 cells or patient-derived intestinal organoids (derived from IBD subjects and from normal colon) were co-cultured with primary microvascular intestinal endothelial cells. In vitro incorporation of multiple cell types, unidirectional flow and peristalsis-like stretch maintained the stem cell niche while enhancing differentiation. Furthermore, cytokine-mediated perturbation of the epithelial-endothelial barrier was ameliorated by standard of care therapy. Recapitulating an in vivo-relevant niche using microphysiological systems provides a dynamic environment for the interrogation of intestinal biology and pathophysiology, particularly where a complex cellular interplay may be relevant.

1. Sartor RB. Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol. 2006;3(7):390-407.
2. Press B, Di Grandi D. Permeability for Intestinal Absorption: Caco-2 Assay and Related Issues. Current Drug Metabolism. 2008;9(9):893-900.