ALTIS BIOSYSTEMS
Toxicity - RepliGut® Planar
RepliGut® Planar model is a unique in vitro model of the intestinal epithelium, which provides a critical barrier against luminal pathogens and is essential for efficient nutrient absorption.
Historically, cell cytotoxicity assays are conducted using model cell lines that are useful for characterizing non-specific drug toxicities at high doses. Intestinal off-target effects are the most common adverse events in Phase I clinical trials and often reflect biology specific to the GI tract, which are not represented in common cell lines. RepliGut® Planar model is a unique in vitro model of the intestinal epithelium, which provides a critical barrier against luminal pathogens and is essential for efficient nutrient absorption. A damaged gut epithelium can lead to significant potential adverse events, therefore understanding the toxicity of compounds is essential prior to in vivo trials. The RepliGut® Planar model provides a physiologically relevant, primary-cell derived intestinal epithelial monolayer that can be used to investigate cell health through a variety of established read-outs, including assays focused on barrier function, cytokine secretion, and gene and protein expression.
Read how the platform can be used to assess GIT risk in early development – here
The RepliGut® Difference
Capitalizes on Unique Aspects of RepliGut® Planar
- High-throughput assay format allows testing of many variables on one plate
- Sequential culture model allows the ability to investigate Proliferative or Differentiated Cells
- Confluent monolayer allows for physiologically relevant, side specific dosing of test articles
Utilizes Relevant/Functional Assays for Toxicity
- Transepithelial electrical resistance (TEER) can be used to indirectly measure barrier function
- Flux of fluorescent dextrans can be used to measure monolayer permeability
- Quantification of % EdU-positive nuclei can be used to measure changes in cell proliferation rates
- LDH Quantification can be used to measure cytotoxicity of differentiated monolayers
- Supernatant and cell lysate collection allows for the samples to be shipped back to the client for customized in-house analysis
Altis Offers Services and Kits
- Assays are Customizable based on client needs
- Consultative, client-focused project design for all client services
- Standard and customized cell culture offerings are available
- Kits are available for shipment, with technical support available
RepliGut® Planar
The monolayer format produces a continuous layer of stem or differentiated cells on a flat and porous surface.
Each tissue sample on the patent-pending RepliGut® kit features a biomimetic scaffold, which separates RepliGut® cells from the cassette’s porous membrane and allows RepliGut® cells to survive for a prolonged period. Without the RepliGut® scaffold, stem cells cannot survive on the cassette.
Luminal and basal reservoirs allow compounds and additional cell types to interact with the epithelial cells for side specific assays.
RepliGut® Planar was developed to replace Caco-2 cells (cancer cells) and animals, which are currently used as a part of compound screening during preclinical studies, before human testing. This 2D monolayer platform should provide much better results than current methods, since it uses proliferative stem cells and terminally differentiated cells.
RepliGut® Kit
The form factor for RepliGut® kit is a multiwell plate, which can be provided in 12 or 96 well sizes, depending on a scientist's needs. Each well contains a cassette insert with an individual tissue sample.
RepliGut® kits can be purchased with all the materials that scientists need to culture the cells in their own facility, including the transwell multiwell plate, stem cells and media.
Different demographic backgrounds to further enhance study data
Guaranteed ability to work with the same donor for years
Multiple regions available from small intestine and colon
Access to primary cells and the crypts
Fit-for-purpose specimens, aligned with scientific objectives
Ethics Committee approved organ procurement