Scaling up human pluripotent stem cell delivery and distribution facilitating reduction in animal use

The award will allow Kate to purchase liquid handling robots and an automated microscope system to increase the capacity of the stem cell facility at the University of Dundee which currently provide cells to 14 research groups – it will enable more researchers to replace animal models in research into neurodegeneration and kidney and heart diseases.

This award was made as part of the 2024 non-animal methods infrastructure grants supported with funding from the Department for Science, Innovation and Technology (DSIT).

Human pluripotent stem cells can be maintained in culture dishes and directed to differentiate into almost any cell type. These cells are therefore powerful tools for studying human development and disease and they provide an opportunity to reduce and replace research using animal models. Working with tissues derived from human pluripotent stem cells overcomes species-specific differences that can limit the translational value of research using animal models. It is further possible to generate patient-specific disease models: human induced pluripotent stem cells can be harmlessly derived from patient skin samples and provide a unique platform to study disease mechanisms. This approach can be complemented by use of precise gene editing technologies, such as the CRISPR-Cas9 system, to create human cells with specific gene alterations that can be used to discover how these changes cause human disease.

Working with human pluripotent stem cells requires in-depth knowledge, technical expertise and dedicated infrastructure to ensure provision of quality-controlled cells for experiments. The Human Pluripotent Stem Cell Facility in the School of Life Sciences, University of Dundee has been providing such cells and supporting researchers to develop differentiation protocols and model human disease for 10+ years. This has led to adoption of these approaches in 21 research groups across the Schools of Life Sciences and Medicine, facilitating transition away from animal models that would be challenging to achieve within individual research groups. This includes models of human neurodegenerative, kidney and heart diseases as well as early human organ development. Gene editing now underpins many of these projects, but the generation of genetically engineered cell lines is labour intensive and time-consuming and this limits the facility’s ability to meet increasing user demand. However, our pipeline is readily amenable to automation.

Here we aim to address the challenge to scale up provision of gene edited human pluripotent stem cells by requesting liquid handling robots, an automated microscope system and an updated electroporation system. This new infrastructure will increase the number of projects the facility can support and pioneer development of a greater range of alternatives to animal models in research. Many facility projects involve researchers working with external collaborators and local biotechnology companies: the potential benefits of the expansion of facility’s capabilities will extend across the university and beyond to the local economy, and as these new disease models become established have the potential to more widely reduce animal use and benefit human health.