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NC3Rs: National Centre for the Replacement Refinement & Reduction of Animals in Research
Project grant

Developing stem cell-derived macrophages to study host pathogen interactions and advance strategies to combat globally important disease in the pig

Test tubes

At a glance

In progress
Award date
November 2020 - July 2023
Grant amount
£350,989
Principal investigator
Dr Thomas Burdon
Institute
University of Edinburgh

R

  • Replacement
Read the abstract
View the grant profile on GtR

Overview

Why did we fund this project?

This award aims to optimise the derivation of macrophages from porcine stem cells for the study of African Swine Fever Virus (ASFV) and Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), replacing the need to isolate macrophages from pigs.

ASFV and PRRSV are highly transmissible diseases with severe economic and welfare implications for the pig farming industry. ASFV has a high mortality rate, and with no vaccine available, containment and culling are the only strategies available for managing an outbreak. PRRSV impacts piglets and pregnant sows, with high morbidity and mortality in piglets and abortions in sows. Both ASFV and PRRSV preferentially replicate in macrophages and are therefore used for research into new treatments or mechanisms of infection. Primary macrophages are the current gold standard but as they do not proliferate in culture, must be continually sourced from sampled or sacrificed animals. Dr Thomas Burdon has developed a system to derive macrophages from pig stem cells. The stem cells can be grown indefinitely, genetically modified in vitro and readily differentiate into macrophages, reducing the reliance on pigs for viral research.

Thomas will optimise the protocol maximising the efficiency of macrophage generation to enable easier uptake of the cells by the virology research community. He will use fluorescent reporter cells to screen culture conditions and monitor the differentiation process. Thomas will also immortalise macrophage progenitor cells, differentiated from the pig stem cells, as novel cell lines enabling faster differentiation into macrophages. All the macrophages developed will be tested for their ability to propagate ASFV and PRRSV and the new protocols for the cells disseminated via a web resource. The technologies developed have wider applications studying further viruses and other pathogens, including bacteria and parasitic pathogens, and could also be applied to other livestock species.

Publications

Meek S et al. (2022). Stem cell-derived porcine macrophages as a new platform for studying host-pathogen interactions. BMC Biology 20: e14. doi: 10.1186/s12915-021-01217-8