The research within our LUMC departments is conducted within departmental research programmes. The research programme below is embedded within the department of Surgery.
Aim and focus
To optimize our ability to assess, improve, and/or repair organs prior to transplantation, and to develop novel immunotherapeutic interventions to improve outcomes. These aims will be investigated in the kidney, pancreas and liver, and will involve the use of ex vivo machine perfusion and biomedical imaging technologies complemented by approaches that include but are not limited to immunology, molecular biology, immunohistochemistry and clinical epidemiology.
Position in international contextSeveral international partnerships have been established, in countries collaborating in Eurotransplant (Belgium, Luxembourg, Germany, Austria, Slovenia, Croatia and Hungary), but also in Canada and the UK, with exchange of knowledge and personnel.
Content / highlights / achievementsThe research of Transplant Surgery has traditionally centred on elucidating the molecular and metabolic pathways of ischemia/reperfusion injury in transplantation and using registry databases to improve our understanding of donor risk indices to model recipient outcomes. The recently established LUMC Transplant Centre and the Organ Preservation and Regeneration Room, both in 2017, has allowed us to initiate the development of new innovative research themes to further our research agenda.
Specific research interests and highlights include:
- Pre-transplant assessment of organ quality through ex vivo machine perfusion using fluorescent imaging, Raman spectroscopy and measurement of biomarkers.
- Designing metabolic salvage strategies to improve transplant outcome. This line of research was recently (2017) awarded an Innovation Call grant from the Dutch Kidney Foundation.
- Development of novel small peptides to protect organs from ischemia/reperfusion injury.
- Participation in clinical trials in organ donation (RELAX) and transplantation (COMPARE and DHOPE), and HPB surgery (POINTER).
- Clinical outcomes research in kidney, pancreas and liver transplantation.
- Response to injury-impaired tissue repair/fibrosis.
We will focus on three main themes: 1) ex vivo machine perfusion, 2) ischemia/reperfusion injury, and 3) transplant outcomes. Examples of topics to be studied within these themes include 1a) regenerative conditioning of organs using mesenchymal stromal cells, 1b) assessing the quality of organs with novel imaging technologies, 1c & 2) assessing the metabolic and mechanistic pathways of ischemia/reperfusion injury, in particular as they relate to energy homeostasis and mitochondrial damage, 2a) understanding the molecular mechanisms dictating impaired tissue repair, and .3) Using national and international registry databases to develop algorithms to optimize donor organ resources. The data generated from these studies will inform the design of future translational clinical trials.
Cohesion within LUMC
The transplant surgery research unit has seen a major overhaul since 2016. Changes have been made to the leadership and the recruitment of several ambitious transplant surgeons has provided the research unit with much-needed resources to help develop a collaborative network of research partners within the LUMC Transplant Centre. Although the LUMC Transplant Centre was initially established in 2017 as an integrated practice unit for clinical care for transplant patients, it has since expanded its scope to include integration of transplant education/training and transplant research. Researchers with a transplant interest at the LUMC have been invited to participate in a working group of the LUMC Transplant Centre to allow for further capitalization of research collaborations with the departments of Vascular Surgery, Nephrology, Hepatology (MDL), Immunohematology and Blood Transfusion (IHB), Clinical Chemistry, Centre for Proteomics &Metabolomics and Pathology, as well as alignment with the Research Profiles Vascular and Regenerative Medicine, Immunity, Infection and Tolerance, and Biomedical Imaging. Existing and future research collaborations with national and international partners will be intensified and developed to further strengthen the position our research enterprise. Based on the recommendations in the mid-term review it was decided to incorporate the vascular research of Dr Lindeman (clinical and molecular aspects of aortic abdominal aneurysm, and the atherosclerotic tissue repository) within that of the transplant surgery research unit.
In 2017 Dr. Ian Alwayn was recruited to provide leadership to the department of transplant surgery. His research interests are complimentary to those traditionally pursued by the transplant surgery research unit and have been integrated into the three main research themes.
1. Ex vivo machine perfusion research: Assess, improve and/or repair organs prior to transplantation.
This is a novel theme within the transplant surgery research unit and relies heavily on the research alignment with the department of nephrology as well as the previous experiences of Dr. Alwayn. Strategies that have previously been validated in animal models will be assessed in pre-clinical studies of ex vivo machine perfusion of human organs. These include quantifying the fat-content of livers prior to transplantation with Raman Spectroscopy, assessing the pre-transplant organ quality with fluorescent imaging, measuring mitochondrial DAMPS in perfusates, and perfusing organs with mesenchymal stem cells or specifically designed cell-penetrating peptides to mitigate and repair organ damage.
Researchers: Dr. Alwayn, Dr. Erdmann, Dr. Huurman, Dr. Doppenberg (postdoc)
Prof. Ton Rabelink, LUMC
Prof. Marlies Reinders, LUMC
Dr. Marten Engelse, LUMC
Dr. Alex Vahrmeijer, LUMC
Prof. dr. Rutger Ploeg, Oxford University
Dr. Boris Gala-Lopez, Dalhousie University
Dr. Kevin Hewitt, Dalhousie Üniversity
Prof. dr. James Shapiro, University of Edmonton
Dr. Steven Paraskevas, McGill University
Dr. Markus Selzner, University of Toronto
2. Ischemia/reperfusion & response to injury/tissue regeneration research.
Ischemia and reperfusion is an unavoidable aspect of organ transplantation. Our research unit has made several important discoveries that highlight the importance of metabolism and mitochondria in the injury that occurs during ischemia and reperfusion in organ transplantation. The mechanisms of injury will be further elucidated with a focus on metabolism in human kidney grafts and the pathways through which mitochondria can modulate the innate and adaptive immune responses.
Molecular aspects of response to injury & tissue regeneration. Response to injury: our work implies differential impacts of ischemia/reperfusion injury on grafts from brain death and cardiac death donors, with a superior recovery potential in grafts from cardiac death donors. We will dedicate part of our research efforts to exploration of possible underlying molecular pathways. Fibrosis is the end stage of impaired tissue repair and organ failure, and a key obstacle for regenerative strategies. Based on extensive earlier work in the abdominal aortic aneurysm it was decided for a shift in our AAA research focus from injury-based focus (inflammation/proteases) to the molecular mechanisms underlying defective compensatory repair. (fatty degeneration and perpetuation of fibrotic responses).
Researchers: Dr. Alwayn, Dr. Lindeman, Dr. Schaapherder, Dr. de Vries (fellow transplant surgery)
Prof. dr. Jaap Hamming, LUMC
Prof. Thomas Hankemeier, LACDR
Prof. Bob van de Water, LACDR
Dr. Jaap Bakker, LUMC
Dr. Saranto Kostidis, LUMC
Dr. Rob Wüst, AMC
Prof. dr. Jean Marshall, Dalhousie University
Dr. Jeannette Boudreau, Dalhousie University
3. Transplant outcomes.
Using registry data to identify risk factors for transplantation, and help develop algorithms to predict outcomes has been another successful theme within the transplant surgery research unit. With the increasing age and rate of co-morbidities of our population, the quality of the organs we have available for transplantation is deteriorating. We are in need of robust models to reduce the number of organs that are unnecessarily discarded for transplantation. Our research group will therefore continue to study these important questions with a focus on the liver and pancreas. Close collaborations with Eurotransplant and the Nederlandse Transplantatie Stichting will be maintained.
Researchers: Dr. Braat, and Dr. Schaapherder
Prof. dr. Jaap Hamming, LUMC
Prof. dr. Hans de Fijter, LUMC
Prof. dr. Eelco de Koning, LUMC
Prof. dr. Bart van Hoek, LUMC
Prof. dr. Hein Putter, LUMC
Dr. Esther Bastiaannet, LUMC
Prof. dr. Robert Porte, UMCG
Prof. dr. Herold Metzelaar, Erasmus MC
Dr. Undine Samuel, Eurotransplant
Prof. dr. Xavier Rogiers, Gent University
Prof. dr. Markus Guba, Munich University
Prof. dr. Rutger Ploeg, Oxford University