Animals have long been used by medical researchers to advance human healthcare, and will be for many years to come.

However, scientists across the UK and the world are working on new techniques to refine, reduce and replace the use of animals in the lab, for example, by attempting to utilise human-derived stem cells or by employing insects and zebrafish in place of mammals.

The National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) is one organisation that supports this field of research. It is currently providing funding of more than £1.7 million to eight projects at the University of Glasgow.

The quest to replace animals in the lab is not driven simply by ethical concerns and empathy for the creatures involved, but by the need for more accurate models of human disease, convenience and greater cost efficiencies.

Ethical, safety and practical concerns often mean animals must stand in our stead, but scientists at Glasgow are developing new models that can help reduce the numbers of animals involved in research and lead to the faster development of successful treatments.

Among the NC3Rs-funded projects at Glasgow is a study aiming to cultivate stem cells derived from leukaemia patients that can be tested in the lab, rather than transplanted into mice.

Led by Dr Helen Wheadon of the Paul O’Gorman Leukaemia Research Centre, part of the Institute of Cancer Sciences, this avenue of research has recently received three years funding from the Dr Hawden Trust.

Leukaemia is a form of cancer which develops from the mutated stem cells of white and red blood cells, called haematopoietic stem cells (HSCs).

Dr Wheadon said: “At present, there is no single model system which accurately replicates human leukaemia in the laboratory. The most acceptable models are in vivo animal models using transgenic mouse models or mice which have deficient immune systems which then have human leukaemia cells transplanted in them.

“However these models are not ideal, and often the leukaemia which develops does not exactly replicate the human disease. This means a lot of drug therapies fail to get past the pre-clinical trials phase.”

The researchers will take HSCs from both healthy donors and leukaemia patients at different stages of the disease and then adapt them so they become induced pluripotent stem cells (iPSCs).

These iPSCs will contain the same disease-sustaining mutations as the original patient but will also have the ability to be a renewable source of the disease-sustaining cancer stem cells, thereby providing a humanized disease model for early drug screening.

These models once developed and validated have the potential for high-through-put drug screening thereby; increasing discovery of drugs with therapeutic potential, significantly reducing the number of animals used in leukaemia research, speeding up the time from discovery to clinical trial and making the process more cost-effective.

To validate their use in future drug trials, it needs to first be proven that adaptations made to the primary HSCs to create iPSCs does not change their response to drugs, which could give misleading test results.

If the researchers can do this they can then proceed to answer the pressing questions: what makes some leukaemia cells resistant to current chemotherapies? How can we predict whether a patient will respond to treatment? What novel targets can be identified for the development of new drugs?

Another researcher who has received funds from NC3Rs is Professor Sue Barnett, who has demonstrated a new model for studying damage to the central nervous system that might help in the development of treatments for diseases like multiple sclerosis and methods of repairing spinal cord injury.

Her most recent project which finished last year and was published in the journal Glia and in the British Journal of Pharmacology. She showed that cells in a Petri dish can be used successfully in the lab to model spinal cord injury without needing to use animal models. NC3Rs funding is still ongoing to continue this work.

She said: “Spinal cord injury is very complex and it is thought that treatments will involve a combination of many strategies including drugs, growth factors and even cell transplantation to replace damaged cells.

“To test these combinations would normally require large numbers of animals using a procedure that requires a Home Office animal licence.

“We wanted to show that mixtures of central nervous system cells could be grown in Petri dishes that could mimic spinal cord injuries. What we saw was many features in the cells in the dish that are seen in animal models, including lack of nerve growth and the loss of the nerve’s insulating myelin sheath. We validated this model by adding drugs known to promote repair in animals and saw similar features.

“This model has lots of advantages, not least of all that it doesn’t involve injuring animals and doesn’t require a Home Office licence.”

Animal research has helped, and continues to, achieve important breakthroughs in healthcare such as treatments for asthma, Parkinson’s disease, cancer, AIDS, meningitis and polio, to name a few.

They will likely be used for many years to come, when testing whether a drug compound is safe to use before administering it to a human. However if reliable alternative models can be developed as a replacement in the lab, this will lead to refinement in the animal models used and will significantly reduce the numbers of animals required in the future.

 

Further information

Funded research at the University of Glasgow:

NC3Rs

  • 1. A three-dimensional air-liquid interface airway epithelial cell model to study pathogen interactions within the bovine respiratory tract
    Dr Robert Davies, University of Glasgow (£390,050)
  • 2. Development of an in vitro screening system to minimise animal use in the search for factors that modulate (re)myelination
    Dr Julia Edgar, University of Glasgow (£73,355)
  • 3. The development of an in vitro model of spinal cord injury to study aligned neurite outgrowth
    Professor Sue Barnett, University of Glasgow (£90,000)
  • 4. The development of an in vitro model of CNS injury to identify factors which promote repair
    Professor Sue Barnett, University of Glasgow (£294,404)
  • 5. Using induced pluripotent stem cells (iPSC) as a replacement for in vivo models to screen novel therapies which target self-renewal pathways in chronic myeloid leukaemia
    Dr Helen Wheadon, University of Glasgow (£120,000)
  • 6. Using the Drosophila fly intestine to investigate Wnt targets in vivo
    Dr Owen Sansom, University of Glasgow (£350,528)
    7. Implanted imaging laboratories for deep-tissue in vivo imaging
    Professor Andrew Harvey, University of Glasgow (£352,773)
  • 8. An in vitro model to investigate the role of oestrogen and oestrogen metabolism in pulmonary vascular disease; Professor Mandy McLean, University of Glasgow (£90,000)

Dr Hadwen Trust

  • 1. Validation of induced pluripotent stem cells as an acceptable alternative model for pre-clinical drug screening in haematological malignancies
    Dr Helen Wheadon, University of Glasgow (£147,753)

Media enquiries: stuart.forsyth@glasgow.ac.uk / 0141 330 4831

First published: 29 April 2014

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