Improving access to human material for diabetes research

In traditional diabetes research, strains of genetically modified mice and rats are bred specifically for diabetes research because they are thought to mimic diabetes in humans. At a conservative estimate, over 92,000 animals are used in diabetes research per year worldwide. While huge, this figure will also be a gross under-estimation, as it does not account for animals culled during transgenic breeding, which can be substantive, or during project development or unpublished work.

Most of the animals used in UK diabetes research are rodents with either a genetic mutation or those that have been treated with a drug to kill their pancreatic insulin-producing cells. The animals are used for a huge range of studies including the effects of raised glucose and insulin levels on physiology; diabetic wound healing studies; the vascular effects of diabetes; the effects of diabetes on vision; looking at how nerves are damaged by the disease; and the effects of diabetes on pregnancy. All of these studies will have different experimental protocols associated with them.

If we concentrate on diabetic wound healing animal studies, wounds are made in the back, thigh or foot skin of the animals with the diabetes mutation and also control animals that do not have the mutation. These wounds may then have drugs applied to see whether this will speed or slow rates of wound closure. The animals are then killed and their tissues used for the research.

During 2014-2017, we will fund a three-year programme at the Glasgow Caledonian University Skin Research Tissue Bank (STB) to provide human skin tissue and cells that can be used for studies related to diabetes. The STB allows clinical samples to be brought in to their laboratories and was established in 2011 to support diabetes research. The skin tissue used is donated anonymously by patients with and without diabetes.

Using human tissue has many advantages over using tissue from animals – it gives a much better idea of how drugs that are used in the laboratory could be developed into medicines in the future. In addition, the use of human tissue and cells replaces the need for animal experimentation, and reduces the use of animal products in research. The human tissue can be made into 3D models of human skin that can be used to test new drugs in development, such as those that may help in the treatment of diabetic ulcers. Researchers at the Glasgow Caledonian University also have the ability to create human stem cells from skin cells, which can be turned into many different types of cells to use in diabetes research, such as nerve cells and blood vessel cells. The use of these stem cells will also reduce the need for animals to be used in these types of experiments.

The Glasgow Caledonian University STB currently supports several different projects in diabetic wound healing, vascular problems with diabetes, diabetic retinopathy and cellular ageing. Our funding will help the STB to develop new types of human cell models that can replace animal experimentation.

Publications

1. Wise RG, Rogers R, Painter D et al (2002). Combining fMRI with a pharmacokinetic model to determine which brain areas activated by painful stimulation are specifically modulated by remifentanil. Neuroimage 16:999-1014.
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2. Wise RG, Williams P & Tracey I (2004). Using fMRI to quantify the time dependence of remifentanil analgesia in the human brain. Neuropsychopharmacology 29:626-35.
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3. Brooks JC, Zambreanu L, Godinez A et al (2005). Somatotopic organisation of the human insula to painful heat studied with high resolution functional imaging. Neuroimage 27:201-9.
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4. Iannetti GD, Niazy RK, Wise RG et al (2005). Simultaneous recording of laser-evoked brain potentials and continuous, high-field functional magnetic resonance imaging in humans. NeuroImage 28:708-719.
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5. Zambreanu L, Wise RG, Brooks JC et al (2005). A role for the brainstem in central sensitisation in humans. Evidence from functional magnetic resonance imaging. Pain 114:397-407.
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6. Tjandra T, Brooks JCW, Figueiredo P et al (2005). Quantitative assessment of the reproducibility of functional activation measured with BOLD and MR perfusion imaging: Implications for clinical trial design. NeuroImage 27:393-401.
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7. Schweinhardt P, Glynn C, Brooks J et al (2006). An fMRI study of cerebral processing of brush-evoked allodynia in neuropathic pain patients. Neuroimage 32:256-265
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8. Brooks JC & Tracey I (2005). From nociception to pain perception: imaging the spinal and supraspinal pathways. J Anat. 207:19-33.
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9. Langley CK, Aziz Q, Bountra C et al (2008). Volunteer studies in pain research – Opportunities and challenges to replace animal experiments. The report and recommendations of a Focus on Alternatives workshop. Neuroimage 42:467-473.
   PubMed Link