Rutger Ploeg

• MD PhD (Leiden)
• Managing Director at University of Oxford

Surgical trauma induces a complex inflammatory stress response, associated with postoperative morbidity. Patients’ physiological reserve, comorbidity, underlying disease and type of surgery will interrelate with the response. In addition, different anaesthetic agents are shown to have differential effects on this response. We explored the molecular...

Introduction A growing interest in renal normothermic machine perfusion (NMP) has resulted in more clinically available perfusion devices. While all perfusion systems have the same aim, there are significant differences in their circuits, pumps, sensors, and software. Therefore, our objective was to assess the impact of different perfusion protocol...

Background Proteomics and metabolomics offer substantial potential for advancing kidney transplant research by providing versatile opportunities for gaining insights into the biomolecular processes occurring in donors, recipients, and grafts. To achieve this, adequate quality and numbers of biological samples are required. Whilst access to donor sa...

The Quality in Organ Donation (QUOD) whole organ project was funded by the MRC to expand the existing QUOD biobanking initiative to biopsy clinically declined whole pancreata, hearts and lungs from deceased donors. The aim was to create a comprehensive tissue bank to facilitate elucidation of pathways underlying organ injury and repair. NHS Blood a...

Background This study investigates the impact of certification training and liver transplant experience on procurement outcomes of deceased donor liver procurement in the Netherlands. Methods Three groups (trainee, certified, and master) were formed, with further subdivision based on liver transplant experience. Three key outcomes—surgical injury,...

Two common obstacles limiting the performance of data-driven algorithms in digital histopathology classification tasks are the lack of expert annotations and the narrow diversity of datasets. Multi-instance learning (MIL) can address the former challenge for the analysis of whole slide images (WSI), but performance is often inferior to full supervi...

Purpose The organ perfusion solution (perfusate), collected at clinically and temporally significant stages of the organ preservation and transplantation process, provides a valuable insight into the biological status of an organ over time and prior to reperfusion (transplantation) in the recipient. The objective of this study was to assess two bot...

Pancreas preservation for both solid organ and islet transplantation has been quite static since the early days of pancreas transplantation. The development of the UW solution in the 1980s following a novel concept and based on a systematic approach of how static cold storage could be improved by successfully attempting to counteract many undesirab...

Static Cold Storage (SCS) injures the bile duct, while the effect of Normothermic Machine Perfusion (NMP) is unknown. In a sub-study of the COPE trial on liver NMP, we investigated the impact of preservation type on histological bile duct injury score (BDIS). Transplants with at least one bile duct biopsy, either at end of preservation or 1 h post-...

Objective: Mass spectrometry profiling of perfusate samples collected during a phase-3 randomized double-blind paired clinical trial of hypothermic machine perfusion (HMP) with and without oxygen (COMPARE) aimed to provide mechanistic insight into key biological alterations of DCD kidneys during continuous perfusion and inform about future interve...

The advent of Machine Perfusion (MP) as a superior form of preservation and assessment for cold storage of both high-risk kidney’s and the liver presents opportunities in the field of beta-cell replacement. It is yet unknown whether such techniques, when applied to the pancreas, can increase the pool of suitable donor organs as well as ameliorating...

Hypothermic machine perfusion (HMP) provides preservation superior to cold storage and may allow for organ assessment prior to transplantation. Since flavin mononucleotide (FMN) in perfusate has been proposed as a biomarker of organ quality during HMP of donor livers, the aim of this study was to validate FMN as a biomarker for organ quality in the...

Organ availability limits kidney transplantation, the best treatment for end-stage kidney disease. Deceased donor acceptance criteria have been relaxed to include older donors with higher risk of inferior posttransplant outcomes. More granular prediction models, based on deeper resolution organ assessment and understanding of damage processes, coul...

Background Remote Ischemic Conditioning (RIC) has been proposed as a therapeutic intervention to circumvent the ischemia/reperfusion injury (IRI) that is inherent to organ transplantation. Using a porcine kidney transplant model, we aimed to decipher the subclinical molecular effects of a RIC regime, compared to non-RIC controls. Methods Kidney pa...

Background: In-situ normothermic regional perfusion (NRP) and ex-situ normothermic machine perfusion (NMP) aim to improve outcomes of liver transplantation (LT) using controlled donation after circulatory death (cDCD). NRP and NMP have not yet been compared directly. Methods: In this international observational study, outcomes of LT performed be...

Donor kidney assessment may improve organ utilisation. Normothermic Machine Perfusion (NMP) has the potential to facilitate this advance. The mechanism of action is not yet determined and we aimed to assess mitochondrial function during NMP. Anaesthetised pigs (n = 6) had one kidney clamped for 60 min. The healthy contralateral kidney was removed a...

Hypothermic machine perfusion (HMP) has become the new gold standard in clinical donor kidney preservation and a promising novel strategy in higher risk donor livers in several countries. As shown by meta-analysis for the kidney, HMP decreases the risk of delayed graft function (DGF) and improves graft survival. For the liver, HMP immediately prior...

Background: In kidney transplantation, the relative contribution of various donor, procedure and recipient-related factors on clinical outcomes is unknown. Previous paired studies have largely focused on examining factors predicting early outcomes, where the effect of donor factors is thought to be most important. Here, we sought to examine the re...

Two common obstacles limiting the performance of data-driven algorithms in digital histopathology classification tasks are the lack of expert annotations and the narrow diversity of datasets. Multi-instance learning (MIL) can be used to address the former challenge for the analysis of whole slide images (WSI) but performance is often inferior to fu...

Assessment of specific β-cell death can be used to determine the quality and viability of pancreatic islets prior to transplantation and hence predict the suitability of the pancreas for isolation. Recently, several groups have demonstrated that unmethylated insulin (INS)-DNA is correlated to β-cell death in type 1 diabetes patients and during clin...

In brain death, cerebral injury contributes to systemic biological dysregulation, causing significant cellular stress in donor kidneys adversely impacting the quality of grafts. Here, we hypothesized that DBD kidneys undergo proteolytic processes that may deem grafts susceptible to post-transplant dysfunction. Using mass spectrometry and immunoblot...

Kidney transplantation is the best renal-replacement option for most patients with end-stage renal disease. Normothermic machine preservation (NMP) of the kidney has been studied extensively during the last two decades and implemented in clinical trials. Biomarker research led to success in identifying molecules with diagnostic, predictive and ther...

Background: Pancreas and islet transplantation outcomes are negatively impacted by injury to the endocrine cells from acute stress during donor death, organ procurement, processing, and transplant procedures. Here, we report a novel electron microscopy scoring system, the Newcastle Pancreas Endocrine Stress Score (NPESS). Methods: NPESS was adap...

Despite decennia of research and numerous successful interventions in the preclinical setting, renal ischemia reperfusion (IR) injury remains a major problem in clinical practice, pointing towards a translational gap. Recently, two clinical studies on renal IR injury (manifested either as acute kidney injury or as delayed graft function), identifie...

Static cold storage (SCS) is the standard method for pancreas preservation prior to transplantation; however, it does not permit organ assessment. Normothermic reperfusion (NR) is utilized clinically for other organs to assess viability. Our aim was to develop NR using normothermic machine perfusion technique to simulate reperfusion at the time of...

Assessment of donor kidney quality is based on clinical scores or requires biopsies for histological assessment. Noninvasive strategies to identify and predict graft outcome at an early stage are, therefore, needed. We evaluated the perfusate of donation after brain death (DBD) kidneys during nonoxygenated hypothermic machine perfusion (HMP). In pa...

Background Remote Ischemic Conditioning (RIC) has been proposed as a therapeutic intervention to circumvent the ischemia/reperfusion injury (IRI) that is inherent to organ transplantation. Using a porcine kidney transplant model, we aimed to decipher the subclinical molecular effects of a RIC regime, compared to non-RIC controls. Methods Kidney pa...

Background: Normothermic machine perfusion (NMP) protocols using blood-based solutions are commonly used in the assessment of kidneys before transplantation. This procedure is, nevertheless, limited by blood availability and warrants the search for alternatives. We compared a blood-based solution with a serum-like preservation solution (Aqix) enri...

Background. In brain death, cerebral injury contributes to systemic biological dysregulation, causing significant cellular stress in donor kidneys that adversely impacts the quality of grafts. Here, we hypothesized that DBD kidneys may undergo proteolytic processes that renders grafts susceptible to post-transplant dysfunction. Material & Methods....

Maintaining organ viability between donation and transplantation is of critical importance for optimal graft function and survival. To date in pancreas transplantation, static cold storage (SCS) is the most widely practiced method of organ preservation. The first experiments in ex vivo perfusion of the pancreas were performed at the beginning of th...

Importance: Continuous hypothermic machine perfusion during organ preservation has a beneficial effect on graft function and survival in kidney transplant when compared with static cold storage (SCS). Objective: To compare the effect of short-term oxygenated hypothermic machine perfusion preservation (end-HMPo2) after SCS vs SCS alone on 1-year...

Liver retrieval and preservation are key steps in the transplantation pathway. Both steps are of fundamental importance in providing the best chance of a successful transplant. On arrival at the donor hospital, the retrieval team should introduce themselves to the local team, review all relevant documentation, and agree the retrieval process before...

Objectives: Despite the wider acceptance of expanded criteria kidneys and the advances in immunosuppression, clinicians remain sceptical when it comes to accepting kidneys from significantly older donors, especially for the young adult recipient population (age ≤40 years). Materials and methods: We utilized prospectively maintained data from the...

Normothermic machine perfusion (NMP) is emerging as a novel preservation strategy. During NMP, the organ is maintained in a metabolically active state that may not only provide superior organ preservation, but which also facilitates viability testing prior to transplantation, and ex-situ resuscitation of marginal kidney grafts. While the prevailing...

Background: Coagulation factors may inform on liver function during normothermic machine perfusion (NMP). We investigated whether graft ischemic injury impairs the accumulation of (anti)coagulation factors during NMP of porcine and human livers. Methods: Dynamics of FV, FVII, FVIII, FIX, FX during NMP and their correlation with graft injury was in...

Normothermic machine perfusion (NMP) is emerging as a novel preservation strategy. During NMP, the organ is maintained in a metabolically active state that may not only provide superior organ preservation, but which also facilitates viability testing prior to transplantation, and ex-situ resuscitation of marginal kidney grafts. While the prevailing...

Background: In an era where global kidney shortage has pushed the field of transplantation towards using more marginal donors, modified kidney preservation techniques are currently being reviewed. Some techniques require further optimization before implementation in full scale transplantation studies. Using a porcine donation after circulatory dea...

Donation after circulatory death (DCD) donors are a unique group of patients who do not fulfil the conventional classification of brain death but in whom further resuscitation or treatment is considered futile. Once cardiac arrest and the cessation of circulation has been confirmed, either due to unsuccessful resuscitation or planned withdrawal of...

Normothermic machine perfusion (NMP) of injured kidneys offers the opportunity for interventions to metabolically active organs prior to transplantation. Mesenchymal stromal cells (MSCs) can exert regenerative and anti‐inflammatory effects in ischaemia‐reperfusion injury. The aims of this study were to evaluate the safety and feasibility of MSC tre...

Methods We've created a new resource for pancreatic research quality assessed with standardised pathology reporting Problem statement: Why do pancreas researchers face challenges using normal human pancreatic tissue, when biobanking is a gold standard in many areas?

Background Remote ischaemic conditioning (RIC) is currently being explored as a non-invasive method to attenuate ischaemia/reperfusion injuries in organs. A randomised clinical study (CONTEXT) evaluated the effects of RIC compared to non-RIC controls in human kidney transplants. Methods RIC was induced prior to kidney reperfusion by episodes of ob...

The pancreas is particularly sensitive to acute cellular stress, but this has been difficult to evaluate using light microscopy. Pancreatic ischaemia associated with deceased organ donation negatively impacts whole-organ and isolated-islet transplantation outcomes. Post-mortem changes have also hampered accurate interpretation of ante-mortem pancre...

We describe a proteomics analysis to determine the molecular differences between normothermically perfused (normothermic machine perfusion, NMP) human kidneys with urine recirculation (URC) and urine replacement (UR). Proteins were extracted from 16 kidney biopsies with URC (n = 8 donors after brain death [DBD], n = 8 donors after circulatory death...

Background Deceased donor kidneys are preserved in cold hypoxic conditions. Providing oxygen during preservation might improve post-transplant outcomes, particularly for kidneys subjected to greater degrees of preservation injury. This study aimed to investigate whether supplemental oxygen during hypothermic machine perfusion (HMP) could improve th...

Background aims: Early allograft dysfunction (EAD) following liver transplantation (LT) negatively impacts graft and patient outcomes. The Liver Graft Assessment Following Transplantation (L-GrAFT7) risk-score estimates 3-month graft-failure-free survival (area under the receiver operator characteristic [AUROC] curve=0.83), and was superior to the...

Background: Mesenchymal stromal cell (MSC) therapy may improve renal function after ischemia-reperfusion injury in transplantation. Ex vivo renal intraarterial administration is a targeted delivery method, avoiding the lung vasculature, a known barrier for cellular therapies. In a randomized and blinded study, we tested the feasibility and effecti...

Background: The renal endothelium is a prime target for ischemia-reperfusion injury (IRI) during donation and transplantation procedures. Mesenchymal stromal cells (MSC) have been shown to ameliorate kidney function after IRI. However, whether this involves repair of the endothelium is not clear. Therefore, our objective is to study potential rege...

Pre-transplant normothermic machine perfusion (NMP) of donor kidneys offers the unique opportunity to perform active interventions to an isolated renal graft prior to transplantation. There is increasing evidence that mesenchymal stromal cells (MSCs) could have a para-/endocrine regenerative effect on ischaemia-reperfusion injury. The purpose of th...

The use of kidneys donated after circulatory death (DCD) remains controversial due to concerns with regard to high incidences of early graft loss, delayed graft function (DGF), and impaired graft survival. As these concerns are mainly based on data from historical cohorts, they are prone to time-related effects and may therefore not apply to the cu...

Purpose of review: To summarize recently published studies of preservation strategies including machine perfusion in pancreas transplantation. Recent findings: The shortage of conventional donors is leading units to use extended criteria donors (ECDs) and donors after cardiac death (DCD). Static cold storage (SCS) is still the standard method of...

Background: Abdominal Normothermic Regional Perfusion (aNRP) for donation after circulatory death (DCD) is an emerging organ preservation technique that might lead to increased organ utilization per donor by facilitating viability testing, improving transplant outcome by early reversal of ischemia, and decreasing the risk of unintentional surgical...

Background The renal endothelium is a prime target for ischemia reperfusion injury (IRI) during donation and transplantation procedures. Mesenchymal stromal cells (MSC) have been shown to ameliorate kidney function after IRI. However, whether this involves repair of the endothelium is not clear. Therefore, our objective is to study potential regene...

Background: The renal endothelium is a prime target for ischemia reperfusion injury (IRI) during donation and transplantation procedures. Mesenchymal stromal cells (MSC) have been shown to ameliorate kidney function after IRI. However, whether this involves repair of the endothelium is not clear. Therefore, our objective is to study potential regen...

Background & Aim Renal endothelium is damaged by ischemia reperfusion injury (IRI) during transplantation as a result of the hypoxic metabolism and the resumption of oxygen supply after reperfusion. It has been shown that mesenchymal stromal cells (MSC) are effective in enhancing kidney function after IRI. However, the cellular targets and mechanis...

The study compares urine recirculation (URC) to urine replacement (UR) with Ringer's lactate in a porcine normothermic kidney machine perfusion (NMP) model using a preclinical prototype device. Methods: Kidney pairs were recovered uninjured (as live-donor nephrectomy) and perfused consecutively. Pig kidneys (n = 10) were allocated to either NMP w...

There is good evidence to support the use of Hypothermic Machine Perfusion (HMP) over static cold storage as the favoured preservation method for deceased donor kidneys. However, the utility of HMP as a tool to assess the viability of kidneys for transplant is unclear. There is a need to determine whether perfusate biomarkers produced during HMP ca...

Early graft loss (EGL) is a feared outcome of kidney transplantation. Consequently, kidneys with an anticipated risk of EGL are declined for transplantation. In the most favorable scenario, with optimal use of available donor kidneys, the donor pool size is balanced by risk of EGL, with a tradeoff dictated by the consequences of EGL. To gauge the c...

Ischemia and reperfusion injury (IRI) is a complex pathophysiological phenomenon, inevitable in kidney transplantation and one of the most important mechanisms for non- or delayed function immediately after transplantation. Long term, it is associated with acute rejection and chronic graft dysfunction due to interstitial fibrosis and tubular atroph...

Older people are being increasingly referred for considerations for pancreas transplantation (PT). We investigated the outcomes after PT in our older recipient cohort to establish if offering transplantation to this cohort is justified. A prospectively‐maintained database was interrogated. The cohort was analysed for associations between outcome an...

This review article focuses on current clinical outcomes with novel perfusion strategies in organ transplantation. Broadly, these approaches can be divided into in-situ regional perfusion in the donor and ex-situ machine perfusion of individual organs. In both settings hypothermic and normothermic techniques are in clinical use. Evidence from full...

This pilot study aimed to maintain acceptable animal welfare in the development of a porcine autotransplantation model with severe and incremental renal ischemic injury, a model for usage in future intervention studies. Secondary aims were to develop and test methods to collect blood and urine without the need to restrain or use sedative and avoid...

Normothermic machine perfusion (NMP) of kidneys offers the opportunity to perform active interventions, such as the addition of mesenchymal stromal cells (MSCs), to an isolated organ prior to transplantation. The purpose of this study was to determine whether administering MSCs to kidneys during NMP is feasible, what the effect of NMP is on MSCs an...

The regenerative capacities of mesenchymal stromal cells (MSCs) make them suitable for renal regenerative therapy. The most common delivery route of MSC is through intravenous infusion, which is associated with off-target distribution. Renal intra-arterial delivery offers a targeted therapy, but limited knowledge is available regarding the fate of...

Introduction: Clinical adoption of normothermic machine perfusion (NMP) may be facilitated by simplifying logistics and reducing costs. This can be achieved by cold storage of livers for transportation to recipient centres before commencing NMP. The purpose of this study was to assess the safety and feasibility of post-static cold storage NMP (pSC...

Ex-situ normothermic machine perfusion (NMP) of transplant kidneys allows assessment of kidney quality and targeted intervention to initiate repair processes prior to transplantation. Mesenchymal stromal cells (MSC) have been shown to possess the capacity to stimulate kidney repair. Therefore, the combination of NMP and MSC therapy offers potential...

Background: Hypothermic machine perfusion (HMP) has become standard care in many center's to preserve kidneys donated after circulatory death (DCD). Despite a significant reduction in metabolism at low temperatures, the remaining cellular activity requires oxygen. Because of the role and safety of oxygen during HMP has not been fully clarified, it...

Successful preservation of kidney allografts must counteract the cellular damage evolving after brain death or circulatory arrest. Static cold storage is the simplest method and has therefore been the most widely used. Several preservation fluids have been specially designed for this purpose, but a number of other fluids have been co-opted from oth...

Background: Transplantation of beta cells by pancreas or islet transplantation is the treatment of choice for a selected group of patients suffering from type 1 diabetes mellitus. Pancreata are frequently not accepted for transplantation, because of the relatively high vulnerability of these organs to ischemic injury. In this study, we evaluated t...

Three-dimensional hydrogels are ideal for tissue engineering applications due to their structural integrity and similarity to native soft tissues; however, they can lack mechanical stability. Our objective was to develop a bioactive and mechanically stable hydrogel for clinical application. Auricular cartilage was decellularised using a combination...

Background: Cerebral injury during Donation after Brain Death (DBD) may induce systemic damage affecting long-term kidney function posttransplantation. Conventional evaluation of donor organ quality as a triage for transplantation is of limited utility. Methods: We compared donor kidneys yielding opposing extremes of the continuum of posttranspl...

Ischaemia and reperfusion injury (IRI) is the leading cause of acute kidney injury (AKI), which contributes to high morbidity and mortality rates in a wide range of injuries as well as the development of chronic kidney disease. The cellular and molecular responses of the kidney to IRI are complex and not fully understood. Here, we used an integrate...

Background: Currently, there is no consensus on which treatments should be a part of standard deceased-donor management to improve graft quality and transplantation outcomes. The objective of this systematic review was to evaluate the effects of treatments of the deceased, solid-organ donor on graft function and survival after transplantation. Me...

Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maint...

Transportable normothermic kidney perfusion for 24 hours or longer could enable viability assessment of marginal grafts, increased organ utilization and improved transplantation logistics. Eleven clinically‐declined kidneys were perfused normothermically, six from donors after brain stem death (DBD, median cold ischemia time 33±36.9 hours) and five...