Patients with diabetes are receiving a cutting edge treatment in Oxford which could end their dependence on insulin injections, thanks in part to research at Oxford University, backed up by a new state-of-the-art facility at the Churchill Hospital, part of the Oxford Radcliffe Hospitals. The new facility, based in the Oxford Centre for Diabetes, Endocrinology and Metabolism, has been built with a £1.2 million grant from the Diabetes Research and Wellness Foundation (DRWF). The award was made to the Nuffield Department of Surgery, whose researchers are spearheading the cure for insulin-dependent diabetes.
The technique, many aspects of which were originally pioneered by researchers from Oxford University and more recently optimised by the team in Edmonton in Canada, allows surgeons to transplant islets, the clusters of cells in the pancreas which produce insulin, into patients with type I diabetes. Currently, patients can have regular injections of insulin which keep symptoms of diabetes at bay but do not necessarily prevent serious complications in later life such as blindness, kidney failure, and heart disease. Or patients can undergo a whole pancreas transplant, which is very successful in adults, but involves a major operation which is not suitable for children.
Mr Paul Johnson, Director of the Oxford Islet Transplant Programme and Reader in Paediatric Surgery at the University of Oxford said: “This new facility is a major step forward in enabling us to develop this treatment for diabetes and to understand what causes diabetes in the first place. Researchers from around the world will be attending the opening to learn more about our work.”
The new technique, currently in adult human trials, involves extracting pancreatic islets from the pancreases of organ donors and injecting them directly into a patient’s liver using X-ray to guide the needle. After a successful transplant, patients produce their own insulin in exactly the same way as people without diabetes, and are freed from dependence on daily insulin injections. The aim is to be able to offer this treatment to children within the next five to ten years.
While the transplantation of the islets is relatively straightforward, extracting the islets from the donor pancreas has been the real challenge – a challenge being met by the new facility, the leading centre in the UK and one of the very best in Europe. One of the distinguishing features of the new facility is its ultra-cleanliness. Mr Paul Johnson, Director of the Oxford islet Transplant Programme and Reader in Paediatric Surgery at the University of Oxford, says: “The new facility offers a new level of cleanliness that we have previously not encountered. The staff isolating the islets have to progress through a series of rooms with ever increasing levels of hygiene. Each has higher air pressure than the last so that no contaminants can pass into it, making it much cleaner than the cleanest parts of a normal operating theatre or laboratory. Not even water is allowed inside the rooms as this might be a source of infection.”
Lab technicians must wash and change into scrubs just as a surgeon would before entering the first room, but to enter the last room in the chain, they have to don a full body suit which allows no part of their body to come into contact with the surroundings. An incoming pancreas would progress through the rooms, being passed from one to the other through airlocks, progressing through the various stages of preparation necessary for islet extraction.
The extraction itself takes between four and six hours. First an enzyme is injected into the donated pancreas, which separates the surrounding pancreatic tissue from the islets and breaks it down to make a pancreas digest (a sort of ‘pancreas soup’). This is then put through a process called ‘density separation’ until a sufficient number of pure islets can be recovered. This extraction process isn’t simple, however. “Knowing when you’ve reached the required level of islet separation within the solution takes considerable expertise, gained over many years,” says Mr Johnson. “The experience of the islet isolation team is really important, but even with the expertise we have at this centre, the process is still quite inefficient. We are, therefore, researching ways of improving the number of islets we can extract from each pancreas.”
Another crucial aspect of the research within Oxford is investigating ways to prevent recipients rejecting the donated islets. Adults can be given drugs that suppress their immune system, but the long-term use of these drugs in children would have significant complications. There are various ways that could be used to get round this problem, such as manipulating the recipients’ ‘T-cells’ (cells that play a crucial role in the immune response), using artificially created capsules in which the islets sit, or modifying the islets themselves. The goal is to be able to perform islet transplants without the need for any anti-rejection drugs. The team is also investigating the possibility of creating islets from adult stem cells or genetically modified animal cells.
The extensive research programme takes place at the same time as continuing to treat patients. “Our overall aim is to be able to treat children soon after their diagnosis,” says Mr Johnson. “By taking the results of our clinical trials in adults back into the laboratory and using them to expand our knowledge, we drive forward our research, which will, in turn, improve our clinical practice. The work in this facility keeps Oxford at the forefront of this research and will take us much closer to finding a cure for diabetes in the future.”
Sarah Bone, Executive Director of the Diabetes Research & Wellness Foundation, adds: “This facility is a huge advancement and will allow Oxford to remain at the forefront of islet cell technology. We are proud to be associated with such a highly regarded team and are confident that the facility will become regarded as a centre of excellence, providing much hope and benefit to people with diabetes. DRWF would like to acknowledge the generosity of their supporters, without whom funding of this project would not have been possible.”
The new centre is based within the Oxford Centre for Diabetes, Endocrinology, and Metabolism (OCDEM), a University research centre located at the Churchill, an NHS hospital. OCDEM is itself physically linked by a corridor to the hospital’s Transplant Centre. For more on OCDEM, see www.ocdem.ox.ac.uk