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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 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 rampant negative systemic effects, so 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.

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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.

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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.

RepliGut® Planar Tissue Sample

RepliGut® tissue constructs are polarized monolayers that express tight junction proteins and can be tailored to be comprised of stem/progenitor cells, differentiated cells, or both. All major cell lineages in physiologic ratios can be achieved.

Planar
SMALL INTESTINE Duodenum, Jejunum COLON Transverse

Multiple Donor Biobank

Unrivaled biobank with multiple donors, allows customers to choose regional specificity of the small intestine and colon from donors of different demographic backgrounds to further enhance study data. Fit-for-purpose specimens, aligned with scientific objectives, and the guaranteed ability to work with the same donor for years.

Different demographic backgrounds to further enhance study data

Different demographic backgrounds to further enhance study data

Guaranteed ability to work with the same donor for years

Guaranteed ability to work with the same donor for years

Multiple regions available from small intestine and colon

Multiple regions available from small intestine and colon

Access to primary cells and the crypts

Access to primary cells and the crypts

Fit-for-purpose specimens, aligned with scientific objectives

Fit-for-purpose specimens, aligned with scientific objectives

Ethics Committee approved organ procurement

Ethics Committee approved organ procurement

More platforms currently under development.
To purchase a RepliGut® Kit, please contact us.