As part of our 3D in vitro assay offering, we have developed intestinal and liver organoid models, based on the Hans Clevers method. The well-established models can be used to assess the effect of novel therapeutic agents on normal tissue to predict the in vivo response, typically of off target/off tissue toxicities.

Multiple therapeutic agents can be quickly and efficiently screened using a small volume of agent where in vivo screening might not be possible.

Intestinal Organoid Model Description

Intestinal organoids contain the stem cells that regenerate the tissues and recapitulate many of the features of the in vivo structure, including all differentiated cell types. They therefore enable the in vitro study of the tissue response – from general effects on proliferation and cell death through to effects on particular cell types, transport and signalling pathways.

Intestinal organoids are taken from established cultures and plated in multi-well plate formats to allow assessment of test agents. Their effects on organoid viability and production of crypt-like branching structures are routinely assessed via visual scoring, alongside cell proliferation assays.

Candidates evaluated to date include Wnt regulators, cytokines / growth factors, steroids, lectins and kinase inhibitors.

Readouts

  • Viability and proliferation
  • Immunohistochemistry
  • In situ hybridisation (RNAscope)
  • Cytokine profiling
  • Flow cytometry
  • Gene expression (NGS, array, PCR from whole organoids or selected cell types)

Liver Organoid Model Description

Liver organoids are grown from mouse hepatic duct fragments and plated in multi-well plate formats to allow assessment of test agents. Their effects on organoid viability and uptake of rhodamine 123 are routinely assessed to assess biliary function, alongside cell proliferation assays.

They provide an in vitro culture system for studying hepatic stem and progenitor cells enabling the study of the tissue response – from general effects on proliferation and cell death through to effects on hepatic progenitor cells or hepatic ducts. Growth of hepatic organoids enables convenient in vitro characterisation of the hepatic epithelium in a physiologically relevant system and reduces the need for animal use.

Candidates evaluated to date include transporter-targeted drugs, steroids, farnesoid X receptor agonists and antagonists.

Readouts

  • Viability and proliferation
  • Immunolabelling (immunohistochemistry and immunocytochemistry)
  • Flow cytometry
  • CYP3A4 activity induction
  • Gene expression (NGS, array, qPCR)
  • Cytokine profiling
  • Rhodamine 123 uptake
  • Measurement of reactive oxygen species (ROS)

Research Applications

  1. Predict the in vivo response to treatment
    a. Assess effect on biliary function and liver metabolism
    b. Induced liver toxicity
    c. Proliferation and differentiation
  2. Identify target cells
  3. Define the biological and molecular mechanism of action

Epistem has world-renowned expertise in adult epithelial tissue and stem cell biology, developing and validating novel preclinical models for drug screening.

In vitro organoid services are provided under a licence agreement with the Hubrecht Organoid Technologies (HUB).

Hubrecht Organoid Technology

Human intestinal organoid

Human intestinal organoid

Murine Liver organoid

Murine liver organoid

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3D Organoid Model?

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Contact us via

info@epistem.co.uk

+44 (0)161 850 7600

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