Investigate mechanisms of colon inflammation and immune cell recruitment to discover novel and targeted anti-inflammatory drug candidates in a human-relevant, Organ-on-a-Chip model.
Colon Intestine‑Chip Overview
Established preclinical intestinal models of physiological and inflammatory processes lack certain features necessary for translation to human responses
The Colon Intestine-Chip is the only model to incorporate pre-qualified biopsy-derived primary human organoids and colonic endothelial cells with mechanical forces to emulate in vivo physiology. The model has been demonstrated to emulate inflammatory processes starting at the selective recruitment of immune cells from vasculature, migration to tissue, activation, downstream effector function such as cytokine release, and tissue response including barrier damage. The Colon Intestine-Chip provides the necessary level of complexity to discover and validate novel, targeted drugs and combinatorial therapeutic strategies for IBD.
A comprehensive colonic barrier model
Mechanical forces on the Colon Intestine-Chip provide a more in vivo-relevant environment. Under dynamic conditions, cells differentiate into characteristic populations and structures, creating the intestinal barrier and forming microvilli. This is in contrast with conventional cell culture with limited and largely undifferentiated cell populations and a lack of physical stimuli.
Human-based advanced cell model
Through the combination of biopsy-derived colonoids and colonic endothelial cells, the Colon Intestine-Chip supports more human-like responses, overcoming species differences in animal models that impede human translation.
In vivo-like transcriptome profile
The transcriptome profile of the Colon Intestine-Chip better resembles human colon tissue compared to organoids, with significant enrichment of gene pathways for epithelial cell differentiation, metabolism, and ion transportation.
Physiologically relevant morphology
Mechanical forces of the Colon Intestine-Chip produce increased epithelial polarization and differentiation similar to adult human colon tissue, unlike organoids alone which lack key characteristics of a mature phenotype.
Contains diverse range of epithelial cells
Cellular heterogeneity representative of in vivo physiology is captured with the Colon Intestine-Chip due to the organoid cell source, with improved differentiation and maturation in the chip compared to organoids in suspension.
Relevant barrier function
The Colon Intestine-Chip has a functional barrier with well-defined tight junctions and low permeability. Traditional in vitro models lack relevant barrier function needed for studies beyond routine drug absorption.
Application: IMMUNE CELL RECRUITMENT
IBD research is limited by the inability of conventional models to model complex human immune response.
Inflammatory bowel disease (IBD) is driven by the dysregulation of immune cell recruitment, which results in a runaway inflammatory cascade and damaging downstream effects. This complex immune response is difficult to model in conventional in vitro models because of their limited complexity, and animal models, meanwhile, have been shown to be poor predictors of human immune response due to species differences. The Colon Intestine-Chip addresses these challenges by offering an unparalleled window into the complex mechanisms of human immune response in IBD.
Gain an unparalleled window into IBD with the only colon- and inflammation-specific model of human immune cell recruitment
By administering peripheral blood mononuclear cells (PBMCs) in the vascular channel in the presence of a pro-inflammatory priming stimulus, researchers can create a highly holistic, human- and colon-specific recapitulation of immune cell recruitment and downstream response. This includes immune cell adhesion to the endothelium and migration into the tissue, activation of complex interstitial immune signaling networks, and finally a release of the critical hallmark cytokines and disruption of the epithelial barrier, all in a single, human-relevant model.
Evaluate the efficacy of immune cell targeted anti-inflammatory drugs
The Emulate Colon Intestine-Chip can be applied to study the efficacy and mechanism of action of drug candidates targeting the recruitment of PBMCs from vasculature to the gut luminal tissue. Emulate has tested multiple clinically relevant compounds with different mechanisms of action and shown how they can block PBMC recruitment, reduce downstream effector function, and prevent PBMC-induced barrier damage.
Application: CYTOKINE-MEDIATED inflammation
Investigate mechanisms of inflammation and evaluate efficacy of anti-inflammatory drug candidates
The complexity of the intestinal niche and poorly understood inflammatory mechanisms make developing novel therapeutics for diseases related to colon inflammation a challenge. Current models such as Caco-2 Transwells do not express some of the key inflammatory cytokines associated with diseases like inflammatory bowel disease. There is a lack of available treatments that are safe, effective, and produce durable responses, presenting a need for improved preclinical models for better clinical translation. The Colon Intestine-Chip can help address this need by enabling mechanistic studies of cytokine-mediated barrier disruption.
Recreate key mechanisms of colon barrier disruption
By administering proinflammatory cytokines, colonic barrier inflammation can be modeled in a concentration-, time-, and donor-dependent manner, with measurable outcomes including, proinflammatory cytokine secretion, enrichment of inflammatory gene pathways, barrier disruption, and apoptosis.
Assess the efficacy of anti-inflammatory drugs
The Emulate Colon Intestine-Chip can be applied to study the efficacy of anti-inflammatory drug candidates to prevent or treat cytokine-mediated inflammation and barrier disruption. Prophylactic treatment with a marketed anti-inflammatory has been shown to inhibit the inflammatory phenotype, reducing the release of proinflammatory cytokines and blocking or delaying barrier damage.
Part of the Human Emulation System®
The Human Emulation System is comprised of instruments, consumables, and software in a flexible, open format. The user-friendly platform gives researchers a window into the inner workings of human biology.
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Experience the predictive power of Organ-on-a-Chip technology. Gain deeper insights by incorporating the Colon Intestine-Chip in your lab workflow or having our team of scientists design and execute a study to meet your needs.
Technical Note: Characterization of the Colon Intestine-Chip
Lear how organoids and Organ-on-a-Chip technology work together to create the most comprehensive commercially available model of the colonic barrier.
Modeling Inflammation-Specific Immune Cell Recruitment in the Colon Intestine-Chip
Utilizing the Colon Intestine-Chip to Investigate Mechanisms of Gastrointestinal Disease
Presented by Mark Donowitz, PhD – LeBoff Professor of Medicine and Physiology, The Johns Hopkins University School of Medicine, Athanasia Apostolou, PhD – Research Scholar, Emulate
Modeling Inflammatory Immune Cell Recruitment and Response with the Colon Intestine-Chip
Presented by Chris Carman, PhD – Director of Immunology, Emulate