Pump Priming Research Awards
Below are the names of recipients together with a brief description of their research projects. Each project will last approximately 12 months at the end of which the recipient will write a report on their research and the outcome. These reports will be available on our website as soon as they become available.
2021
Hussain Abbas
Global assessment of liver function during normothermic machine perfusion in high-risk donor livers
Normothermic machine perfusion (NMP) provides the opportunity to assess liver function outside the body prior to transplantation. Current tests only provide an idea of liver injury which may not represent the entire liver. A novel test (Maximal Liver Capacity, LiMAx) has been used to determine liver capacity in patients undergoing liver surgery and transplant in order to predict outcomes. This is particularly relevant for high-risk livers (those with excess fat within liver cells) that are associated with poor post-transplant outcomes. We will investigate if LiMAx could be useful in providing a global assessment of such livers for transplantation during NMP.
Mohammed Elzawahry
Using machine preservation to improve pancreas transplantation (PTx).
Diabetes results from insufficient insulin production by the pancreas. It leads to complications including blindness, kidney failure, amputation and heart disease which can significantly shorten life.
Pancreas transplantation can be an effective treatment option in diabetic patients with the most severe complications, however many donor pancreases are not used due to concerns about their quality. My aim is to test pancreases using a device that pumps fluid and oxygen
through the organ prior to transplantation. This research has the potential of increasing the number of patients who can benefit from PTx and improving the safety profile of this treatment.
Richard Dumbill and John Mulvey
Temperature manipulation during kidney preservation
Over 7000 patients in the UK begin regular dialysis each year due to kidney failure. A kidney transplant is usually preferable to dialysis as it offers significant benefit with respect to quality of life, and life expectancy. Prior to transplant, kidneys are usually stored on ice then transplanted as soon as possible. Normothermic machine perfusion is a novel method for preserving kidneys prior to transplantation that offers substantial potential benefits. This study looks at how best to rewarm kidneys ahead of transplantation to minimise damage and aims to closely examine the effects of temperature and oxygen availability on kidney metabolism.
Alexander Sagar
Prolonging Liver Preservation at Body Temperature
Transplantation remains the main treatment for liver failure. There are 11,000 people with liver transplants in the UK. Unfortunately, 12% of patients on the waiting list either die, or are de-listed due to deterioration, whilst awaiting transplantation. Although traditionally organs have been stored on ice, storage at body temperature with a continuous supply of nutrients enables organ recovery during preservation. This increases the proportion of organs that can be transplanted. This proposal would extend the body-temperature preservation period from hours to days. This will improve organ assessment to maximise utilisation and facilitate treatments that enhance graft function prior to implantation.
Rachel Thomas
Novel technique to improve donor kidneys?
Demand for kidney transplants exceeds supply so research aims to improve the quality of marginal deceased kidneys. Normothermic Regional Perfusion (NRP) is a novel retrieval technique used in two UK centres with a proven positive impact on donor livers. The consequences for NRP kidneys are less well established but may provide better quality organs and therefore, improve outcomes for the 5000 patients on the transplant waiting list. This innovative research will investigate whether NRP impacts on kidney tissue and, if there is evidence of an improved appearance, this could recommend expansion of NRP programmes.
2020
Syed Hussain Abbas
The utility of hand-held near infrared micro-spectrometry in predicting the severity of steatosis in human livers procured from deceased donors.
The success of liver transplantation is limited by waiting list deaths of up to 20%. Donor shortages necessitate the need to
optimise high-risk fatty organs. However, current methods of estimating the liver fat content are not well validated. The utility of
technology based on spectrometry will enable greater identification donor fatty livers with more than 30% fat. These organs may
benefit from organ preservation outside the body on a machine with delivery of defatting agents due to their high risk.
Identification and optimisation of such organs will reduce discard rates and improve post-transplant outcomes. For full report click here
Matthew Bottomley
Circulating Monocytes as a Predictor of Cancer Risk in Long-Term Renal Transplant Recipients.
Up to a quarter of kidney transplant patients develop cancer within twenty years of transplant. Cancer after transplant may progress more rapidly and have poorer outcomes compared with cancer in non-transplant patients.
We previously identified a marker in a type of white blood cell (‘monocyte’) which is associated with increased future risk of developing cancer in kidney transplant recipients. We will study this in more depth to understand how its presence is associated with elevated cancer risk.
Better understanding of risk factors behind post-transplant cancer marker may identify new interventions to predict and prevent cancer in transplant patients. For full report click here
Tamsyn Clark
Isolated liver chemoperfusion: For cancer and beyond
For every 100 patients whose bowel cancer has spread to the liver, only 14 will be alive five years after their diagnosis. Treatment options for these patients are limited and cause distressing side effects including nausea, tiredness and hair loss. For full report click here
Richard Dumbill
Effect of the age of blood in ex-vivo normothermic machine perfusion.
Blood donations are stored for up to 35 days before being used for transfusion (for severe anaemia), or to preserve organs ahead of transplantation. Blood stored for longer periods of time may be a less effective treatment than blood stored for short periods of time. We plan to investigate whether older blood can provide enough oxygen to tissues by measuring tissue oxygenation in kidneys perfused with blood of various ages. This will help us understand which units of blood can be used for preserving organs for transplantation, for treating patients with anaemia, and how to prevent stored blood deteriorating. For full report click here
Georg Ebeling
Improving the Outcomes after Liver Transplantation
Liver transplantation is the only definitive treatment for patients with end-stage liver disease. Ongoing shortages of donor organs
result in accepting livers from older or multimorbid donors, which is associated with poorer outcomes. Therefore, marginal livers can
be isolated and preserved on a perfusion machine, which provides nutrients and oxygen at body temperature, resulting in improved
liver function. We aim to take advantage of this technique and to simultaneously deliver drugs such as nucleic acids prior to
transplantation. This will probably lead to reduced organ damage, subsequently resulting in less complications and reduced treatment
costs for the NHS
Fungai Dengu and Sotiris Masoridis
Therapeutic applications of Extracellular vesicles (EVs) in normothermic machine perfusion (NMP) of livers: towards targeted immune modulation and organ reconditioning.
Extracellular vesicles (EVs) are nano-sized ‘bubbles’ released by cells and carry ‘cargo’ such as proteins and genetic code, enabling communication between cells and the regulation of immune responses. Due to their stability and the ability to select which cargo to load them with, their potential as a therapeutic agent is enormous. Translation to patients has been hindered by an inability to get them where they need to act (donor organ) without being taken up in other sites. This study will explore the uptake and distribution of EVs delivered directly to isolated donor livers during machine perfusion. For final report
Etohan Ann Ogbemudia
Laboratory biomarkers to aid the diagnosis of pancreatitis and rejection in Pancreas Transplantation.
Pancreas transplantation (PT) is an established operation to treat type 1 Diabetes Mellitus. During the period of organ retrieval, pancreases are without a blood supply - this phenomenon is called ischemia. Ischemia predisposes pancreases to have pancreatitis and this can cause significant complications including an increased risk of rejection.
Currently, there are no reliable investigations to diagnose pancreatitis or rejection until it is too late.
We have identified some well-known blood tests successfully used in other conditions that we suspect could be diagnostic biomarkers. These tests would be vital to alert clinicians to provide necessary early interventions. to prolong the lifespan of PT. For full report click here
Sushma Shankar
Analysis of longitudinal immunity in SARS-CoV-2-convalescent patients with a renal transplant or haemodialysis.
66000 patients with end stage renal failure (ESRF) in the UK require renal replacement therapy (RRT) such as renal
transplantation or haemodialysis, to survive. However, ESRF and haemodialysis result in immune compromise whilst transplant
recipients need immunosuppression, leaving these patients vulnerable to severe infection and ineffective vaccination. Such
patients have an increased risk of death from COVID-19 compared to the general population. This work aims to determine
whether RRT patients who recover from COVID-19, develop sustained immune responses which offer protection from future reinfection.
Such findings may also inform vaccine strategies in these patients. Final report click here
2019
S H Abbas
Clinical Research Fellow in Transplantation
The impact of normothermic machine perfusion and defatting on Hypoxia-Inducible Factor (HIF) expression in human steatotic livers
HIF expression during normothermic machine perfusion
The success of liver transplantation is limited by waiting list deaths of up to 20%. Donor shortages necessitate the need to optimise high-risk fatty organs. This can be achieved by organ preservation outside the body (normothermic machine perfusion) and delivery of defatting agents. Such organs are vulnerable to low oxygen levels resulting in activation of hypoxia inducible factors (HIFs) which have may have an acute protective effect. The research on HIF expression during normothermic machine perfusion in context of therapeutic defatting interventions is needed understand their expression, acute protective mechanisms and subsequent influence on post-transplant outcomes. For full report click here
J Branchereau
Researcher
Pancreas Perfusion Programme: Comparison of hypothermic preservation methods in donor pancreases
Pancreas Perfusion Program: a way to improve the donor pancreas during storage
Diabetes impacts the lives of 415 million people worldwide and is predicted to rise to 642 million by 2040. Pancreatic transplantation saves the lives of human patients suffering incontrollable and debilitating diabetes on a daily basis. There remains a shortage of donor organs which has created a driving pressure to achieve an optimal approach for organ preservation in the organs utilized for transplantation. Following cooling of organs in ice, introducing machine perfusion with oxygen could improve transplantation success rates. This study concludes the final step before this method of perfusion is introduced in human transplantation. For full report click here
F Dengu
Clinical Research Fellow and DPhil Candidate
Determining the capacity of therapeutic cells delivered during normothermic perfusion of the liver to engraft within donor organs
Tracking cellular therapies given during NMP
Immunosuppression after transplantation is associated with a substantial personal and societal burden owing to their toxic effects which include cancer, infections and renal failure, as well as the high financial costs. Cellular therapies offer hope for minimization of these medications but often fail to reach the target organ when given systemically. Giving these new therapies during NMP may be a solution, however crucial work on the feasibility of delivering these cells is urgently required. We propose to label and track cells that are delivered during NMP to determine their capacity for engraftment within the target organ. For full report click here
F M Elgilani
Clinical Research Fellow
Safety and efficacy of Tofacitinib in ameliorating ischaemia reperfusion injury and allograft pancreatitis in solid organ transplantation – a pilot study
Medication to reduce transplant pancreatitis
40-50% of patients who have a pancreas transplant can develop an inflammatory life threatening condition called pancreatitis. This condition makes patients stay in hospital longer and remain more unwell. It also reduces graft survival. To prevent this complication, we want to use an anti inflammatory therapy, blocking a key molecular switch that drives the inflammation. We will be using a medication called Tofacitinib which has been used in patients with autoimmune inflammatory diseases such as rheumatoid arthritis and ulcerative colitis. We believe we will be able to dampen the effect, which will improve patient's outcome and graft survival. For gull report click here
2018
Matthew Brook
NIHR Academic Clinical Lecturer
Assessment of cell therapy in Transplantation
Approximately 5,000 patients received a kidney transplant in the UK last year and are required to take life-long anti-rejection medications. These are highly effective but have significant side effects.
We are using natural cells from the blood called Tregs, expand in number in the laboratory, to protect a kidney transplant from rejection and reduce the need for anti-rejection medications.
This ground-breaking study aims to discover whether, following Treg infusion into the kidney transplant recipients, we can identify these cells within the kidney transplant itself and prove that they are working to prevent rejection. Full report click here
Ann Ogbemudia
Research and Clinical Fellow in Transplantation
Islets in skin to treat diabetes
Diabetes Mellitus is a condition where a person’s body loses the ability to adjust their blood sugar putting them at risk of strokes, heart attacks, kidney failure, blindness, limb amputations or premature death.
There are currently 3.7million sufferers in the UK and that figure is rising exponentially.
We promise to take human islet cells that naturally regulate blood sugar from deceased donor pancreas where they reside and incorporate them in small pieces of skin which when transplanted would function as a pancreas. This procedure is easily performed, monitored and removed if necessary in this superficial position in the recipient’s forearm. For full report click here
Fungai Dengu
Clinical Research Fellow in Transplant Surgery
Profiling the Liver during machine profusion
Donated livers can now be preserved on a machine that pumps blood and oxygen, medicines and nutrients through it at normal body temperature as opposed to storage ‘on-ice’ which is harmful to the organ, especially in marginal donor organs.
Clinical trials have shown excellent results with this new technology. Using samples collected from these studies, we will investigate what happens to immune cells within the liver during preservation with the machine and explore how we may be able to exploit this knowledge of the immune environment to deliver novel immune treatments that can improve patient outcomes. For full report click here
2017
Katarzyna Dagmara Bera
NIHR Academic Clinical Fellow (Core Training) in General Surgery, ST2
Brain death duration in deceased organ donors
Kidney transplantation provides the ideal treatment for end-stage renal failure and worldwide the demand for organs by far
exceeds the available organ pool. It is thus important to optimise the long-term function and survival of donated kidneys from
deceased donors. This project is designed to characterise changes in the donor’s blood during brain death over time aiming to
understand the systemic stress affecting the kidney before procurement. We want to understand whether any serum biomarkers
can help us to predict which organs will have a good or poor outcome, and identify novel treatment targets to prevent further
injury or initiate repair prior to transplantation. For full report click here