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NC3Rs: National Centre for the Replacement Refinement & Reduction of Animals in Research
Skills and Knowledge Transfer grant

Fully humanised 3D vascular perfused model for breast cancer modelling and therapeutic screening

Blue pipette tips

At a glance

In progress
Award date
October 2019
Grant amount
£75,912
Principal investigator
Professor Valerie Speirs
Institute
University of Aberdeen

R

  • Reduction
  • Replacement

Overview

Why did we fund this project?

This award aims to combine two technologies that avoid the use of animal products in in vitro models of breast cancer, improving the relevance of the models and their potential to replace some xenograft studies in mice. 

A range of in vivo and in vitro models are used to study breast cancer to reflect different types and stages of the disease. Current in vivo models include xenografts and transgenic models. Xenograft models using patient tissue have low engraftment rates (up to 27%) creating a bias of cancers that are studied. Generating the correct mutation in a genetically engineered mouse model is also inefficient as the majority of animals will not have the mutation of interest. These models can be replaced using 3D in vitro models, however these require animal-derived matrices, such as collagen or Matrigel, to sustain the cellular phenotype. Professor Cathy Merry (Co-Investigator, University of Nottingham) has developed a customisable synthetic peptide hydrogel with NC3Rs funding. By adding various extracellular matrix components, such as proteins or sugars, in specific quantities the hydrogel can be composed to represent the environment of a breast cancer tumour in a patient.

To increase the clinical relevance of the hydrogel model, Professor Valerie Speirs and colleagues will combine this technology with their previously developed PerfusionPal platform, also developed with NC3Rs funding. This uses a high-density liquid “blood substitute” to constantly perfuse growing breast cancer cells enabling delivery of therapeutics as if they were administered intravenously creating a vascularised human 3D cell culture system for the study of breast cancer.

This award was made in collaboration with Cancer Research UK.

Publications

  1. Ashworth JC et al. (2020). Preparation of a User-Defined Peptide Gel for Controlled 3D Culture Models of Cancer and Disease. J. Vis. Exp. 166:e61710. doi: 10.3791/61710