Switching to human stem cells to study leukaemia
Human-relevant research into leukaemia
Leukaemia is a cancer of white blood cells and arises due to a genetic change in the normal stem cells that produce blood cells in the bone marrow. Studying the leukaemic stem cells that are produced is challenging as these cells are rare and difficult to isolate.
Mice are usually used to generate the cells needed for leukaemia research; however, human cells can be used instead by reprogramming them in the lab to a basic stem cell state.
Rachel, supervised by Dr Helen Wheadon at the University of Glasgow, has developed a way to grow and support the use of these human cells. Her research has the potential to replace animal products and models in leukaemia research.
The Science behind the studentship
Nanoscale topography for stem cell maintenance and disease modelling of leukaemia
Blood cells are produced in the bone marrow by specialised cells called haemopoietic stem cells (HSC). These produce all the different mature blood cells needed throughout life and have the unique property of being able to divide to form more stem cells or differentiate/mature. Leukaemia is a cancer of white blood cells it arises due to a genetic change in a HSC (transformation). The Leukaemic stem cells (LSCs) have a growth and survival advantage leading to the overproduction of white blood cells and the disease symptoms. Studying LSCs is difficult as these cells are rare and difficult to isolate, only making up <0.01% of the leukaemia cells. It is these cells that are resistant to current therapies.
Recent advances in science have enabled us to reprogram adult cells to a primitive stem cell state, called human induced pluripotent stem cells (iPSC), which we can culture and use to study diseases in the laboratory. However current culture systems are costly and not very robust for long-term iPSC maintenance as many of the surfaces/defined medias result in spontaneous differentiation over time. This has resulted in the stem cell field still relying on the use of animal derived feeder cells and products for long term maintenance. In this project we will use specialist bioengineering approaches to culture our normal and leukaemic iPSCs, in order to circumventing these issues. By developing a bioengineered fully humanised culture system we hope to completely REPLACE the need for animal derived cells and products in the future.
To maximise the potential of iPSCs, robust, fully humanised, bioengineered culture systems need to be developed and validated which comply with good manufacturing practice (GMP) to enable clinical grade iPSC derivation and maintenance. Current methods still depend on mouse embryonic fibroblasts (mEFs). In the last 5 years, 55 studies in the UK and 903 studies Worldwide (PubMed) have used mEFs as a supportive feeding layer for various types of PSCs. Given this involves sacrificing at least 2 pregnant mice and all the embryos (4-8 embryos on average/mouse) per batch of mEF’s produced, for a 3 year research project most groups would require at least 3 batches per year.
This project aims to develop our novel bioengineered nanonetworks in order to characterise and validate a fully humanised culture system for iPSC maintenance, which can then be further refined to comply with GMP for clinical applications in the future. We are passionate about replacing animals in science and feel this is a research area where REPLACEMENT is easily achievable in the future by new cross-disciplinary methodologies.