Animals spared in new cancer tests on cells

SCOTTISH researchers have developed new cell techniques to replace animal testing in the study of serious conditions including cancer and spinal injuries.

Almost £1 million has been invested in the latest efforts by Glasgow University scientists to address ethical concerns about animal testing and improve research methods to make them more relevant to human health.

In one study which has just started, researcher Dr Helen Wheadon and her team are using innovative stem-cell techniques to create new ways of testing drugs for leukaemia, rather than relying on laboratory mice.

Campaigners welcomed the latest work to refine and reduce the use of animals in medical research, but said some animal work would still be needed to ensure new treatments could be safely tested in humans.

The Glasgow researchers have received funding from the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) and the Dr Hadwen Trust, which also supports work to replace the use of animals in research.

Figures show that in 2012 some four million animals, including mice, dogs and birds, were used in scientific research in Britain.

Wheadon and her team, which includes Prof Mhairi Copland and Prof Tessa Holyoake, have received funding of almost £150,000 as part of their latest efforts to develop better ways of testing treatments for leukaemia without having to use as many animals.

This form of cancer develops from mutated stem cells in the body’s white and red blood cells, known as haematopoietic stem cells (HSCs).

Stem cells are very early stage cells, often called the building blocks of the body, which are the focus of much research in the hope that they can be used to regenerate damaged tissue and in the testing of new treatments.

Researchers looking at leukaemia can get small numbers of HSCs for testing in samples from patients, but they mostly rely on genetically modified mice when investigating potential new drugs.

But Wheadon said this had a number of disadvantages which meant new treatments could fail to progress to further testing.

“At present there is no single model system which accurately replicates human leukaemia in the laboratory,” she said.

“The most acceptable models are 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,” said Wheadon.

“This means a lot of drug therapies fail to get past the pre-clinical trials phase.”

The researchers have so far taken cells from four healthy donors and three patients with chronic myeloid leukaemia (CML) and using a special cocktail of four proteins succeeded in turning them back into early stage cells, known as induced pluripotent stem cells (IPS cells).

These cells contain the same mutations which sustain the disease in patients with leukaemia but also have the ability to renew, giving researchers an limitless supply of cells on which to experiment. These cells can then be used for the early screening of new drugs, rather than relying on mice.

Wheadon said they would now be going on to make sure that the cells they had created had not been altered in a way that made them different to other patient cells, testing drugs on them to see if they respond in the same way.

She said testing drugs on these early cells was important because current treatments failed to get to cancerous stem cells in bone marrow which sustained the disease.

While other researchers have created IPS cells from leukaemia patients, the Glasgow team is believed to be among the first to try to use the technology to test new drugs.

The researchers also hope to be able to use the cells to identify which patients respond well to treatment and which do not, meaning new combination therapies can be developed.

Wheadon said animals would still need to be used for final safety and toxicology tests before drugs were tested in humans, but they hoped to use fewer mice in the earlier stages of research.

Brett Cochrane, group head of science at Dr Hadwen Trust, said the work being done on leukaemia in Glasgow was “excellent” and there is now “huge scope to replace the number of animals that are being used.”

He said figures showed that more than 20,000 mice were used annually in research on leukaemia alone in the UK and while some animal use would still be required, reducing that number was important.

Another study being carried out in Glasgow with the hope of reducing the use of animals is focusing on how to repair damage to the central nervous system, which could help in the search for treatments for diseases like multiple sclerosis and repairing spinal cord injury.

Professor Sue Barnett and her team last year published research showing that cells in a petri dish can be used as a model for spinal cord injury without having to use animals.

She said treatments for complex spinal cord injuries would need to involve a combination of techniques including drugs and cell transplants to successfully treat them. But she said testing these combinations would normally require large numbers of animals in procedures which required special Home Office animal licences.

“We wanted to show that mixtures of central nervous system cells could be grown in petri dishes that could mimic spinal cord injuries,” Barnett said.

“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.”

Libby Anderson, from the Edinburgh-based animal protection group One Kind, welcomed the move, saying: “Animal testing has led medical research down many blind alleys over the years, and caused untold animal suffering.

“This makes it hugely encouraging to see the increased use of human cells to replace animals. Stem cells must give a more accurate model for testing drugs and modelling the development of disease, and they can be reproduced in the laboratory to provide a supply of identical material.

“As the range of alternatives increases it becomes more and more difficult to justify using animals and this is a very welcome development.”

Dr Vicky Robinson, chief executive of the NC3Rs, said the centre prioritised funding projects that it felt had the greatest potential to minimise the use of animals and improve animal welfare in scientific research.

“There are several interesting projects going on in Scotland at the moment, which promise real 3Rs benefits,” she said. “Since 2005 we’ve committed over £5.3m to Scottish research organisations for 3Rs research.”