Investigate mechanisms of colon inflammation and barrier disruption and evaluate the efficacy of anti-inflammatory drug candidates in an organoid-derived 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 organoids and colonic endothelial cells with mechanical forces to emulate in vivo physiology. Through the control of experimental parameters and ease of multiple measurements, the model can be utilized to evaluate biochemical, genetic, and cellular responses in drug safety assessments, physiology and function studies, and disease modeling.
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.
A 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.
Enhanced 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.
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 inflammation
By administering proinflammatory cytokines, colonic barrier inflammation can be modeled in a concentration-, time-, and donor-dependent manner, with measurable outcomes such as:
- Proinflammatory cytokine secretion
- Barrier disruption
- Enrichment of inflammatory gene pathways
- Apoptotic activation
Evaluate 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, including:
- Preventing the loss of tight junctions
- Blocking or delaying barrier damage
- Reducing proinflammatory cytokine secretion
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.
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.