Caption: From left to right: D.Phil. candidates Kexin Yu and Delaney Dominey-Foy, alongside Dr. Pablo F. Céspedes, lead the initial development, benchmarking, and validation of lymphoid organoids, comparing them to lymphoid tissue biopunch explants. In collaboration with Dr. Joannah Fergusson (not pictured), the team is also advancing the benchmarking of precision-cut spleen and palatine tonsil slices.
Mice have long been the preferred model for studying multisystemic immunity. However, accumulated evidence shows that mouse immunology poorly replicates the genetic, biochemical, and physical diversity of humans. The recent development of lymphoid organoids from tonsils and spleens by Professor Mark Davis's group (Stanford Medicine) demonstrates the scientific benefits and predictive power of non-animal, primary human lymphoid organoids. Despite these advantages, broad adoption of these organoids remains challenging due to limited access to fresh human tissue samples and protocols for their use.
The Cespedes lab has successfully adopted this novel tonsil organoid technology and developed a second method for investigating lymphocyte self-organization into ex vivo follicles. Their new system can be primed with recombinant antigens and other growth factors, enabling a wide variety of experimental designs. This approach has replaced the need for genetically modified mouse models, with significant potential to further reduce animal model use.
The award from NC3Rs, made as part of the 2024 non-animal methods infrastructure grants supported with funding from the Department for Science, Innovation & Technology (DSIT), will allow Dr Pablo Cespedes to purchase equipment, consumables and training materials to establish a high throughput facility to generate lymphoid organoids prepared from human tonsil and spleen tissue. This facility should reduce the use of animal models for immunology studies. The aim is to remove barriers to proof-of-principle experiments by providing access to instruments, tissues, recombinant materials, protocols, and hands-on training.
The facility will provide lymphoid organoids for researchers at the University of Oxford and across the UK. To find out more about the hub contact Dr Pablo Cespedes, Pablo.cespedes@ndm.ox.ac.uk.