February 26, 2013 -- Research describing an innovative ‘lung-on-a-chip’ microdevice that can accurately replicate conditions in a diseased human lung has been awarded an international prize for its potential to revolutionise preclinical drug testing by offering a viable alternative to using animals.
Announced today (26th February 2013) by the UK’s National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), the NC3Rs annual 3Rs Prize recognises the most promising scientific advances and technological developments to replace, reduce or refine the use of animals in research and testing.
Developed by Professor Donald Ingber of the Wyss Institute for Biologically Inspired Engineering, at Harvard University (USA), and published in Science Translational Medicine, the microdevice contains hollow channels lined with living human cells, mimicking both the interface between tissues and the unique physical environment seen in whole living organs. Crystal clear and flexible, it is approximately the size of a USB memory stick.
Applying a vacuum to part of the microdevice allows it to ‘breathe’, recreating the way in which our tissues physically expand and contract during respiration. In testing it was able to successfully replicate the conditions seen in pulmonary oedema (fluid accumulation in the lungs), and predict results of a new drug for this life-threatening condition, which showed benefit in animal studies.
In addition, the microdevice has allowed the researchers to carry out real-time high resolution imaging on the cells and make accurate measurements of fluid flow and blood clot formation, which are not easily available in an animal model.
Professor Ingber said: “This is precisely the kind of progress that regulatory government agencies, such as the Food and Drug Administration (FDA) in the US, and pharmaceutical companies need to see in order to seriously consider an alternative approach to animal models.”
In their paper the researchers describe how the next step is to apply the technology to other human organs with the goal of one day being able to use it as part of an automated system to test many drugs. While it is not expected to offer an immediate replacement for animal studies, further development and applications of the technology could allow for a more gradual replacement of animal models of human disease.
Dr Vicky Robinson, Chief Executive, NC3Rs, said: “The NC3Rs annual 3Rs Prize champions the 3Rs globally, rewarding real scientific and technological advances. This technology may be the beginning of a revolution of the systems used to model human disease and test drugs, with great potential to reduce the need for animals. By recognising it with our 3Rs Prize, we hope to expose it to the UK’s scientific community and encourage further research in this area.”
Due to the number of high-quality entries, three other papers have been awarded highly-commended prizes. Scottish-based researcher Professor Susan Barnett, University of Glasgow, was commended for research developing an in vitro model of spinal cord injury using rat embryonic spinal cord cells. This has enabled the laboratory to test the combination of drugs being studied using cells from one animal only, representing a 97% reduction had an established methodology been used. This method is being further developed for testing therapeutics more widely.
London-based Professor Gareth Sanger, Queen Mary, University of London, was commended for research demonstrating the benefit of using human - rather than animal - gastrointestinal tissues for drug testing, which are obtained as part of normal surgical procedures.
US researcher Professor Shuichi Takayama, University of Michigan (USA), was commended for developing a 3D cell culture to test anti-cancer drugs, which proved to be more representative of clinical responses than standard 2D ‘flat’ cell cultures, demonstrating the potential for this method to replace and reduce the use of animals in pharmaceutical testing.
The GlaxoSmithKline-sponsored prize was presented by Professor Paul Matthews, Vice President, Integrative Medicines Development, GlaxoSmithKline, who said: “GlaxoSmithKline is delighted to continue to sponsor this important award. The quality of the submissions this year highlights success in embedding the 3Rs principles in research across the globe. This competition illustrates well how innovative science is being translated rapidly into approaches that can both advance the 3Rs agenda and further develop biomedical science for improved human health.”
For further information:
Dan Richards, Communications Manager, NC3Rs. firstname.lastname@example.org 020 7611 2253. 07920 265 897
Photography is available.
About the NC3Rs 3Rs Prize
The NC3Rs awards an annual prize for an original contribution to scientific and technological advances in the 3Rs (replacement, reduction and refinement of animal use) in medical, biological or veterinary sciences published within the last three years. Sponsored by GlaxoSmithKline, the prize consists of a prize grant of £18k, plus a personal award of £2k, and is part of the NC3Rs’ commitment to recognise and reward high quality research which has an impact on the use of animals in the life sciences. Highly-commended prizes consist of a grant of £4k, plus a personal award of £1k.
How the lung-on-a-chip works:
? Inside the microdevice are two parallel, sub-millimeter sized, hollow channels which are separated by a thin, flexible, porous membrane. This membrane is coated with matrix proteins that normally hold cells together in human tissues.
? One side of this membrane is lined with living human cells isolated from the air sac of a lung, and air is allowed to permeate into the channel to recreate the environment seen in a lung. The other side contains human lung capillary blood cells with a blood-like solution flowing over their surfaces.
? A vacuum applied to side chambers alongside the channels recreates the way our tissues physically expand and retract when we breathe.
? Recreating these conditions has been an important step to develop new insights into human lung disease that are difficult to achieve in with animal studies, such as the ability to carry out high-resolution imaging on the cells themselves, observing blood clot formation and fluid flow.
Supplementary video with animation: http://wyss.harvard.edu/viewpage/240/lungonachip
Winning research paper
? Huh D, Leslie DC, Matthews BD, Fraser JP, Jurek S, Hamilton GA, Thorneloe KS, McAlexander MA, Ingber DE (2012). A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a-chip microdevice. Science Translational Medicine 4 (159): 159ra147.
Highly commended papers:
? Boomkamp SD, Riehle MO, Wood J, Olson MF, Barnett SC (2012). The development of a rat in vitro model of SCI demonstrating the addictive effects of Rho and ROCK inhibitors on neurite outgrowth and myelination. Glia 60 (3): 441–456.
? Broad J, Mukherjee S, Samadi M, Martin JE, Dukes GE, Sanger GJ (2012). Regional- and agonist-dependent facilitation of human neurogastrointestinal function by motilin receptor agonists. British Journal of Pharmacology 167 (4): 763–774.
? Tung YC, Hsiao AY, Allen SG, Torisawa Y, Hoc M, Takayama S (2011). High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array. Analyst 136 (3): 473–478.
About the NC3Rs
The NC3Rs is an independent scientific organisation which leads on the discovery, development and promotion of new ways to replace, reduce and refine the use of animals in research and testing (the 3Rs). It is supported primarily by Government, but also receives funding from the charitable and industrial sectors. The Centre has an annual budget of approximately £6.75 million and is the UK’s major funder of 3Rs research. Further information about NC3Rs activities and programmes can be found at www.nc3rs.org.uk
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