FRAME aims for animal alternatives

By Dr Matt Wilkinson

- Last updated on GMT

Related tags Cell culture

Research into new tools that will remove the need to use animals in
medical research has received a £240,000 (€356,000) boost at the
University of Nottingham.

The £240,000 investment by the FRAME (the Fund for the Replacement of Animals in Medical Experiments) charity and the University of Nottingham will be spent upgrading and expanding a laboratory designed to look for effective and validated alternatives to animal testing.

While the debate over the ethics and validity of conducting experiments on animals still rages, FRAME has been trying to reduce the need for the debate altogether by investing in research that could yield alternative methods to animal testing.

The new laboratory is one of the few laboratories run by such a charity and confirms FRAMEs ambition to remove the need for animal testing while recognising that new medicines and chemicals need to be adequately tested to ensure that they do not harm humans, animals or the environment.

In order to reduce the number of animals used in experiments without jeopardising medical research the FRAME laboratory will try to grow human tissue cultures in which drug candidates can be tested.

"In the short term we're looking at tissue culture replacements, and the first area of research is to get primary human tissue culture started - it is quite rare to grow human cells on a routine and thorough basis such that one could conduct validated toxicological studies," said Dr Andy Bennett, director of the FRAME Alternatives Laboratory.

"Primarily we're looking at hepatocytes because there's a huge interest from big pharmaceutical companies because all drugs known to man have to go through the liver and have to be hepatoxicity tested."

These tissues could help reduce the vast number of rats that get killed during preclinical drug toxicity testing and because the cells would be derived from human cell lines, they have the potential to give more reliable results than animal models in some experiments.

Recent research from the University of Nottingham has shown that animal models do not always mimic human response, even during processes as 'simple' as starvation.

"While there's some very good data from experiments on animals, there is also some shocking data from them as well because there metabolism, gene expression etc is different," said Dr Bennett.

Rather than just using recognised tissue growth culture techniques, the FRAME laboratory is looking at immortalising the cell lines using virus based vectors that will aid cell cycle control and reduce telomere shortening.

The group are doing this using lentiviruses, a type of retrovirus that can deliver a significant amount of genetic information into the DNA of a host cell.

While this means the group won't be producing perfect liver or human skeletal cells, they aim to produce cells that would retain a significant number of the features needed to allow them to become viable alternatives to using animals.

"We will have a variety of cells lines that can do certain jobs, so if you're interested in drug toxicity testing we'll have a cell line available for that," said Dr Bennett.

"We are particularly interested in the intermediary metabolism involved with insulin and glucose regulation and we are trying to develop cell lines that will retain those signalling pathways."

Dr Bennett explained that even when the cell lines are available, expensive validation studies will still need to be conducted before the new lines could be used to replace animal testing "Validation is a real problem, nobody is allowed to change a mode of testing unless it's been properly validated because the FDA [US Food and Drug Administration] just wouldn't accept the results of studies conducted with the cells without validation," said Dr Bennett.

The group will be looking to collaborate with pharmaceutical companies after initial development to help spread the burden of the validation costs.

In the meantime, the researchers will be able to enjoy working in the new molecular cell biology laboratory where they can conduct toxicity testing, gene expression analysis and protein functional measurement.

In addition, they will have access to two new custom built tissue culture laboratories and an analytical chemistry laboratory.

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