Human Enteroids/Colonoids and Intestinal Organoids Functionally Recapitulate Normal Intestinal Physiology and Pathophysiology

Abstract

Identification of Lgr5 as the intestinal stem cell marker as well as the growth factors necessary to replicate adult intestinal stem cell division has led to the establishment of the methods to generate "indefinite" ex vivo primary intestinal epithelial cultures, termed "mini-intestines." Primary cultures developed from isolated intestinal crypts or stem cells (termed enteroids/ colonoids) and from inducible pluripotent stem cells (termed intestinal organoids) are being applied to study human intestinal physiology and pathophysiology with great expectations for translational applications, including regenerative medicine. Here we discuss the physiologic properties of these cultures, their current use in understanding diarrhea-causing hostpathogen interactions, and potential future applications.

A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection

“…Is Reproducible Across HIEs from Different People. HIEs are novel, physiologically active, nontransformed cultures that are increasingly used to study human pathogen-host interactions (5,8,9,39,40). We first evaluated the variability in the transcriptional response to HRV infection in HIEs by analyzing transcriptomes from one jejunal HIE culture by microarray analysis.…”

Intestinal Enteroids Model Guanylate Cyclase C-Dependent Secretion Induced by Heat-Stable Enterotoxins

“…In vitro models (e.g., human colon cancer cells) may not recapitulate normal tissue architecture, biology, or molecular signaling events (13,16,17,19), while in vivo models, such as suckling mice (20) and ileal loops (21), are labor-intensive and not suited to high-throughput screening. These considerations underscore the need for models of intestinal signaling and secretion which are compatible with high-throughput analyses and recapitulate the pathophysiology of ST-induced diarrhea (2,16,17,22,23).…”

“…Stem cells isolated from mouse or human intestinal crypts are propagated in three-dimensional cultures, where they form "miniguts," encompassing the cell types of the mature intestinal epithelium and recapitulating normal intestinal physiology (16,17,24). While enteroids are biologically relevant models for infectious diarrheal diseases (16,17,22,23), their suitability as a platform to study ST-induced intestinal secretion remains unknown (17). Since previous studies demonstrated that pharmacological agents, including complex multimeric proteins like cholera toxin, readily access the lumen of enteroids (25,26), we predicted that these organoids should respond to GUCY2C ligands.…”

Intestinal Organoids—Current and Future Applications

“…To date, human enteroids have been shown to model human rotavirus (RV) infection, cholera toxin effect on transport, and several aspects of enterohemorrhagic Escherichia coli-related human diarrhea. RV replicates and produces infectious viruses in human enteroids and organoids, with viral replication increasing over 96 h [38].…”