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NC3Rs: National Centre for the Replacement Refinement & Reduction of Animals in Research
Partnerships and impact awards

Long-term, self-maintaining primary 3D cultures of mouse and human epithelial tissues for reduction and replacement of animals in research

Grant holder David Fernandez-Antoran sitting at a computer displaying an image of cells.

At a glance

Completed
Award date
June 2022 - May 2024
Grant amount
£74,306
Principal investigator
Dr David Fernandez-Antoran
Institute
University of Cambridge

R

  • Replacement
Read the abstract
View the grant profile on GtR

Overview

Why did we fund this project?

This award aims to share a culture method that enables epithelial cells to be expanded directly from mouse or human tissues across eight laboratories in the UK and internationally.

A range of 3D cellular in vitro models have been developed to further understanding of epithelial tissue and tumour development. Often these models require cells to be isolated from tissue, either animal or human, and while the resulting cultures replicate epithelial tissue architecture, they do not fully mimic other properties such as long-term expansion and self-maintenance. Dr David Fernandez-Antoran has developed an in vitro 3D culture method, called epithelioids, that enables epithelial cells to be expanded directly from mouse or human tissues to study epithelial development and tumour formation. The cultures are self-maintaining for up to a year and can be used in experiments, such as long-term drug studies or to provide cells for other experiments (e.g. for CRISPR/Cas9 genome editing). David has demonstrated his methodology works for multiple epithelial tissues, including oesophagus, skin, bladder and trachea, with tissue-like structures forming in each case avoiding the need to source cells from multiple animals for an experiment. David will now work with researchers from six different institutes to optimise and implement the culture method for their research.

This project was awarded under the skills and knowledge transfer scheme, which ran from 2017 to 2022, supporting the exchange and uptake of models, tools or technologies with immediate and deliverable 3Rs impacts. The NC3Rs continues to provide funding to build new collaborations between developers and end-users through our partnerships and impact awards to catalyse the transfer of 3Rs methods.

Publications

  1. Herms A et al. (2024). Self-sustaining long-term 3D epithelioid cultures reveal drivers of clonal expansion in esophageal epithelium Nature Genetics doi: 10.1038/s41588-024-01875-8