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Quality and Safety in Organ Donation Tissue Bank - Expansion to include Pancreas/Islets, Heart and Lungs

Funder: UK Research and InnovationProject code: MR/R014132/1
Funded under: MRC Funder Contribution: 1,688,840 GBP

Quality and Safety in Organ Donation Tissue Bank - Expansion to include Pancreas/Islets, Heart and Lungs

Description

Organ transplantation saves thousands of lives every year and is the treatment of choice for end stage organ failure. Despite awareness of importance of transplantation, a gulf remains between the supply and need for life-saving organs. This is predicted to worsen over the next decade, making this disparity a key challenge facing the transplant community today. Due to this shortage, nowadays older and higher risk donors are accepted. However, uncertainty as regards transplantability often results in decline and sometimes discard of scarce organs. Between April 2015 and March 2016, 479 patients died waiting for a lifesaving transplant. A further 3,452 patients were temporarily suspended from the waiting list because they were unfit for transplant. The Quality in Organ Donation (QUOD) Biobank was established in 2012. This unique resource combines collection of detailed clinical information from virtually all organ donors in the UK with blood and urine samples taken around the time of donation and carefully collected small biopsies from a range of organs stored within a central 'bank'. This has been invaluable in research focused on understanding how stress associated with becoming an organ donor around the time of death affects control of important whole body systems such as blood pressure and glucose levels in addition to impact on specific organs. This has already enabled otherwise impossible research focused on better selection and optimisation of organs enhancing successful transplantation. The pancreas, heart and lungs work in concert to maintain glucose levels, blood pressure and effective oxygenation throughout life. The extreme stress around the time of death has a major impact on these control systems. Despite a huge unmet clinical need, 'conversion' of these organs into successful transplants is much lower than in kidney transplantation. Impairment and failure of these organs is also central to many of the most common and challenging chronic diseases, including diabetes, heart failure; and lung disease. We propose to expand QUOD to include samples from pancreas, heart and lungs and will work closely with MRC Units to ensure provision to the research community of highest quality state-of-the-art clinical pathology and molecular techniques as well as single cell analysis platforms, in addition to facilities expert in processing organs to retrieve live functioning cells. This will allow us to create detailed atlases and a data library representing the range of normal, acutely stressed and chronically diseased tissues from these organs that can be seldom accessed in life which has severely limited true understanding of mechanisms driving damage and failure. This type of resource linked to such high quality clinical information and a library of new markers associated with these processes and easily monitored from blood samples does not currently exist. The QUOD remit and proposed expansion will be made accessible to the widest possible scientific and clinical community. It will enable new understanding of causes of organ stress, facilitating new treatments to maximise transplant success and ultimately help to prevent / reverse chronic diseases without need for transplantation. In type 1 and 2 diabetes it is becoming clear that insulin-producing cells are not completely destroyed, offering exciting new possibilities for reactivating function which may ultimately lead to a cure for this burdensome and dangerous disease. Deeper understanding of mechanisms underlying heart pump failure will facilitate increased numbers of heart transplants but also new treatments for all with chronic heart failure targeting specific processes damaging the muscle. Elucidation of the causes of scarring lung disease will be accelerated through this resource. Moreover, previously impossible parallel research exploring pathological interplay between pancreas, heart and lungs with already collected data on liver and kidney will be enabled.

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