Machine Perfusion in Organ Transplantation

A special issue of Transplantology (ISSN 2673-3943). This special issue belongs to the section "Solid Organ Transplantation".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 28280

Special Issue Editors


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Guest Editor
1. Department of Hepato-Pancreato-Biliary Surgery, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK
2. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
Interests: transplantation; hepatobiliary; liver cancers

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Guest Editor
Edinburgh Transplant Centre, Royal Infirmary of Edinburgh and University of Edinburgh, Old Dalkeith Road, Little France Crescent, Edinburgh EH16 4SA, UK
Interests: multiorgan transplantation

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Guest Editor
1. Department of Hepato-Pancreato-Biliary Surgery, Freeman Hospital, Newcastle Upon Tyne NE7 7DN, UK
2. Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK
Interests: multiorgan transplantation

Special Issue Information

Dear Colleagues,

Over the last five decades of advancement in transplantation, static cold storage (SCS) of donated organs has remained the standard of care as a vital link in the chain between donor and recipient. As transplant clinicians, we have known for some time that SCS has well-recognized limitationsNow, with the rapidly progressing technology of in situ and ex situ machine perfusion (MP), the prospect of improved preservation, more effective assessment and even reconditioning of organs before transplant is within our reach. While many uncertainties regarding the implementation of this emerging technology remain, we are already observing its impact on transplant medicine globally. By expanding the donor pool and allowing surgeons to assess and successfully transplant organs that once would have gone unutilized, we may change the face of organ transplantation forever. This Special Issue of “Transplantology” will cover all forms of organ perfusion currently in use.  

Prof. Dr. Derek Manas
Dr. Gabriel C. Oniscu
Dr. Colin Wilson
Guest Editors

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Keywords

  • normothermic regional perfusion (NRP)
  • normothermic machine perfusion (NMP)
  • hypothermic machine perfusion (HMP)
  • marginal organs
  • organ assessment
  • persufflation

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Published Papers (8 papers)

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Research

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0 pages, 2843 KiB  
Article
Exploring Porcine Precision-Cut Kidney Slices as a Model for Transplant-Related Ischemia-Reperfusion Injury
by L. Annick van Furth, Henri G. D. Leuvenink, Lorina Seras, Inge A. M. de Graaf, Peter Olinga and L. Leonie van Leeuwen
Transplantology 2022, 3(2), 139-151; https://doi.org/10.3390/transplantology3020015 - 26 Apr 2022
Cited by 7 | Viewed by 2689
Abstract
Marginal donor kidneys are more likely to develop ischemia-reperfusion injury (IRI), resulting in inferior long-term outcomes. Perfusion techniques are used to attenuate IRI and improve graft quality. However, machine perfusion is still in its infancy, and more research is required for optimal conditions [...] Read more.
Marginal donor kidneys are more likely to develop ischemia-reperfusion injury (IRI), resulting in inferior long-term outcomes. Perfusion techniques are used to attenuate IRI and improve graft quality. However, machine perfusion is still in its infancy, and more research is required for optimal conditions and potential repairing therapies. Experimental machine perfusion using porcine kidneys is a great way to investigate transplant-related IRI, but these experiments are costly and time-consuming. Therefore, an intermediate model to study IRI would be of great value. We developed a precision-cut kidney slice (PCKS) model that resembles ischemia-reperfusion and provides opportunities for studying multiple interventions simultaneously. Porcine kidneys were procured from a local slaughterhouse, exposed to 30 min of warm ischemia, and cold preserved. Subsequently, PCKS were prepared and incubated under various conditions. Adenosine triphosphate (ATP) levels and histological tissue integrity were assessed for renal viability and injury. Slicing did not influence tissue viability, and PCKS remained viable up to 72 h incubation with significantly increased ATP levels. Hypothermic and normothermic incubation led to significantly higher ATP levels than baseline. William’s medium E supplemented with Ciprofloxacin (and Amphotericin-B) provided the most beneficial condition for incubation of porcine PCKS. The porcine PCKS model can be used for studying transplant IRI. Full article
(This article belongs to the Special Issue Machine Perfusion in Organ Transplantation)
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0 pages, 1705 KiB  
Article
Development of a Porcine Slaughterhouse Kidney Perfusion Model
by Leonie H. Venema and Henri G. D. Leuvenink
Transplantology 2022, 3(1), 6-19; https://doi.org/10.3390/transplantology3010002 - 28 Dec 2021
Cited by 3 | Viewed by 3314
Abstract
Machine perfusion techniques are becoming standard care in the clinical donation and transplantation setting. However, more research is needed to understand the mechanisms of the protective effects of machine perfusion. For preservation related experiments, porcine kidneys are acceptable alternatives to human kidneys, because [...] Read more.
Machine perfusion techniques are becoming standard care in the clinical donation and transplantation setting. However, more research is needed to understand the mechanisms of the protective effects of machine perfusion. For preservation related experiments, porcine kidneys are acceptable alternatives to human kidneys, because of their size and similar physiology. In this experiment, the use of slaughterhouse kidneys was evaluated with normothermic kidney perfusion (NKP), thereby avoiding the use of laboratory animals. Porcine kidneys were derived from two local abattoirs. To induce different degrees of injury, different warm ischemic times and preservation techniques were used. After preservation, kidneys were reperfused for 4 h with two different NKP solutions to test renal function and damage. The effect of the preservation technique or a short warm ischemic time was clearly seen in functional markers, such as creatinine clearance and fractional sodium excretion levels, as well as in the generic damage marker lactate dehydrogenase (LDH). Porcine slaughterhouse kidneys are a useful alternative to laboratory animals for transplantation- and preservation-related research questions. To maintain kidney function during NKP, a short warm ischemic time or hypothermic machine perfusion during the preservation phase are mandatory. Full article
(This article belongs to the Special Issue Machine Perfusion in Organ Transplantation)
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Review

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15 pages, 2898 KiB  
Review
Normothermic Machine Perfusion as a Tool for Safe Transplantation of High-Risk Recipients
by Manuel Durán, Angus Hann, Hanns Lembach, Anisa Nutu, George Clarke, Ishaan Patel, Dimitri Sneiders, Hermien Hartog, Darius F. Mirza and M. Thamara P. R. Perera
Transplantology 2022, 3(2), 169-183; https://doi.org/10.3390/transplantology3020018 - 10 May 2022
Cited by 2 | Viewed by 2463
Abstract
Normothermic machine perfusion (NMP) should no longer be considered a novel liver graft preservation strategy, but rather viewed as the standard of care for certain graft–recipient scenarios. The ability of NMP to improve the safe utilisation of liver grafts has been demonstrated in [...] Read more.
Normothermic machine perfusion (NMP) should no longer be considered a novel liver graft preservation strategy, but rather viewed as the standard of care for certain graft–recipient scenarios. The ability of NMP to improve the safe utilisation of liver grafts has been demonstrated in several publications, from numerous centres. This is partly mediated by its ability to limit the cold ischaemic time while also extending the total preservation period, facilitating the difficult logistics of a challenging transplant operation. Viability assessment of both the hepatocytes and cholangiocytes with NMP is much debated, with numerous different parameters and thresholds associated with a reduction in the incidence of primary non-function and biliary strictures. Maximising the utilisation of liver grafts is important as many patients require transplantation on an urgent basis, the waiting list is long, and significant morbidity and mortality is experienced by patients awaiting transplants. If applied in an appropriate manner, NMP has the ability to expand the pool of grafts available for even the sickest and most challenging of recipients. In addition, this is the group of patients that consume significant healthcare resources and, therefore, justify the additional expense of NMP. This review describes, with case examples, how NMP can be utilised to salvage suboptimal grafts, and our approach of transplanting them into high-risk recipients. Full article
(This article belongs to the Special Issue Machine Perfusion in Organ Transplantation)
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18 pages, 828 KiB  
Review
Advances in Hypothermic and Normothermic Perfusion in Kidney Transplantation
by Thomas B. Smith, Michael L. Nicholson and Sarah A. Hosgood
Transplantology 2021, 2(4), 460-477; https://doi.org/10.3390/transplantology2040044 - 17 Nov 2021
Cited by 7 | Viewed by 6987
Abstract
Hypothermic and normothermic machine perfusion in kidney transplantation are purported to exert a beneficial effect on post-transplant outcomes compared to the traditionally used method of static cold storage. Kidney perfusion techniques provide a window for organ reconditioning and quality assessment. However, how best [...] Read more.
Hypothermic and normothermic machine perfusion in kidney transplantation are purported to exert a beneficial effect on post-transplant outcomes compared to the traditionally used method of static cold storage. Kidney perfusion techniques provide a window for organ reconditioning and quality assessment. However, how best to deliver these preservation methods or improve organ quality has not yet been conclusively defined. This review summarises the promising advances in machine perfusion science in recent years, which have the potential to further improve early graft function and prolong graft survival. Full article
(This article belongs to the Special Issue Machine Perfusion in Organ Transplantation)
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9 pages, 955 KiB  
Review
Ex Vivo Lung Perfusion: A Platform for Donor Lung Assessment, Treatment and Recovery
by Luke Milross, Chelsea Griffiths and Andrew J. Fisher
Transplantology 2021, 2(4), 387-395; https://doi.org/10.3390/transplantology2040037 - 27 Sep 2021
Viewed by 2889
Abstract
Lung transplantation offers a lifesaving therapy for patients with end-stage lung disease but its availability is presently limited by low organ utilization rates with donor lungs frequently excluded due to unsuitability at assessment. When transplantation does occur, recipients are then vulnerable to primary [...] Read more.
Lung transplantation offers a lifesaving therapy for patients with end-stage lung disease but its availability is presently limited by low organ utilization rates with donor lungs frequently excluded due to unsuitability at assessment. When transplantation does occur, recipients are then vulnerable to primary graft dysfunction (PGD), multitudinous short-term complications, and chronic lung allograft dysfunction. The decision whether to use donor lungs is made rapidly and subjectively with limited information and means many lungs that might have been suitable are lost to the transplant pathway. Compared to static cold storage (SCS), ex vivo lung perfusion (EVLP) offers clinicians unrivalled opportunity for rigorous objective assessment of donor lungs in conditions replicating normal physiology, thus allowing for better informed decision-making in suitability assessments. EVLP additionally offers a platform for the delivery of intravascular or intrabronchial therapies to metabolically active tissue aiming to treat existing lung injuries. In the future, EVLP may be employed to provide a pre-transplant environment optimized to prevent negative outcomes such as primary graft dysfunction (PGD) or rejection post-transplant. Full article
(This article belongs to the Special Issue Machine Perfusion in Organ Transplantation)
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17 pages, 3085 KiB  
Review
Persufflation—Current State of Play
by Aaron John Buhagiar, Leo Freitas and William E. Scott III
Transplantology 2021, 2(3), 362-378; https://doi.org/10.3390/transplantology2030035 - 17 Sep 2021
Cited by 2 | Viewed by 3773
Abstract
With the ever-increasing disparity between the number of patients waiting for organ transplants and the number organs available, some patients are unable to receive life-saving transplantation in time. The present, widely-used form of preservation is proving to be incapable of maintaining organ quality [...] Read more.
With the ever-increasing disparity between the number of patients waiting for organ transplants and the number organs available, some patients are unable to receive life-saving transplantation in time. The present, widely-used form of preservation is proving to be incapable of maintaining organ quality during long periods of preservation and meeting the needs of an ever-changing legislative and transplantation landscape. This has led to the need for improved preservation techniques. One such technique that has been extensively researched is gaseous oxygen perfusion or Persufflation (PSF). This method discovered in the early 20th century has shown promise in providing both longer term preservation and organ reconditioning capabilities for multiple organs including the liver, kidneys, and pancreas. PSF utilises the organs own vascular network to provide oxygen to the organ tissue and maintain metabolism during preservation to avoid hypoxic damage. This review delves into the history of this technique, its multiple different approaches and uses, as well as in-depth discussion of work published in the past 15 years. Finally, we discuss exciting commercial developments which may help unlock the potential for this technique to be applied at scale. Full article
(This article belongs to the Special Issue Machine Perfusion in Organ Transplantation)
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Other

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6 pages, 3048 KiB  
Brief Report
Machine Perfusion of the Human Heart
by Stephen Large and Simon Messer
Transplantology 2022, 3(1), 109-114; https://doi.org/10.3390/transplantology3010011 - 18 Mar 2022
Cited by 1 | Viewed by 2748
Abstract
This brief communication about machine perfusion of potential human donor hearts describes its historical development. Included in the review are both the isolated perfusion of donor hearts retrieved from heart beating and non-heart-beating donors. Additionally, some detail of in-situ (within the donor [...] Read more.
This brief communication about machine perfusion of potential human donor hearts describes its historical development. Included in the review are both the isolated perfusion of donor hearts retrieved from heart beating and non-heart-beating donors. Additionally, some detail of in-situ (within the donor body) normothermic regional reperfusion of the heart and other organs is given. This only applies to the DCD donor heart. Similarly, some detail of ex-situ (outside the body) heart perfusion is offered. This article covers the entire history of the reperfusion of donor hearts. It takes us up to the current day describing 6 years follow-up of these donor machine perfused hearts. These clinical results appear similar to the outcomes of heart beating donors if reperfusion is managed within 30 min of normothermic circulatory determined death. Future developments are also offered. These are 3-fold and include: i. the pressing need for objective markers of the clinical outcome after transplantation, ii. the wish for isolated heart perfusion leading to improvement in donor heart quality, and iii. a strategy to safely lengthen the duration of isolated heart perfusion. Full article
(This article belongs to the Special Issue Machine Perfusion in Organ Transplantation)
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5 pages, 451 KiB  
Technical Note
Novel Kidney Auto Transplantation Technique for Ischemia-Reperfusion Studies
by Michael Olausson, Deepti Antony, Galina Travnikova, Debashish Banerjee and Goditha U. Premaratne
Transplantology 2021, 2(2), 224-228; https://doi.org/10.3390/transplantology2020021 - 11 Jun 2021
Cited by 2 | Viewed by 1964
Abstract
Large animal studies of long-term ischemia reperfusion are hampered by the use of immunosuppressive drugs to inhibit the influence of the allogeneic response. In small animals, this can be controlled by using inbred strains of the animal. For obvious reasons, this is not [...] Read more.
Large animal studies of long-term ischemia reperfusion are hampered by the use of immunosuppressive drugs to inhibit the influence of the allogeneic response. In small animals, this can be controlled by using inbred strains of the animal. For obvious reasons, this is not possible in large animals such as pigs. Since studies in pigs usually are the last step before first-in-man studies, this remains a problem trying to resemble a clinical situation. In the following short paper, we describe a novel auto kidney transplantation model that can be used for long term ischemia reperfusion studies. We also suggest a control setting to balance out the possible influence of an increased surgical trauma. Full article
(This article belongs to the Special Issue Machine Perfusion in Organ Transplantation)
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