Research

13 pages, 2837 KiB

Open AccessArticle

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://0-doi-org.brum.beds.ac.uk/10.3390/transplantology3020015 - 26 Apr 2022

Cited by 7 | Viewed by 2170

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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14 pages, 1727 KiB

Open AccessArticle

Development of a Porcine Slaughterhouse Kidney Perfusion Model

by Leonie H. Venema and Henri G. D. Leuvenink

Transplantology 2022, 3(1), 6-19; https://0-doi-org.brum.beds.ac.uk/10.3390/transplantology3010002 - 28 Dec 2021

Cited by 3 | Viewed by 2756

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

Open AccessReview

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://0-doi-org.brum.beds.ac.uk/10.3390/transplantology3020018 - 10 May 2022

Cited by 2 | Viewed by 2108

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

Open AccessReview

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://0-doi-org.brum.beds.ac.uk/10.3390/transplantology2040044 - 17 Nov 2021

Cited by 6 | Viewed by 5902

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

Open AccessReview

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://0-doi-org.brum.beds.ac.uk/10.3390/transplantology2040037 - 27 Sep 2021

Viewed by 2553

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

Open AccessReview

Persufflation—Current State of Play

by Aaron John Buhagiar, Leo Freitas and William E. Scott III

Transplantology 2021, 2(3), 362-378; https://0-doi-org.brum.beds.ac.uk/10.3390/transplantology2030035 - 17 Sep 2021

Cited by 1 | Viewed by 3316

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

Jump to: Research, Review

6 pages, 3048 KiB

Open AccessBrief Report

Machine Perfusion of the Human Heart

by Stephen Large and Simon Messer

Transplantology 2022, 3(1), 109-114; https://0-doi-org.brum.beds.ac.uk/10.3390/transplantology3010011 - 18 Mar 2022

Cited by 1 | Viewed by 2297

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

Open AccessTechnical 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://0-doi-org.brum.beds.ac.uk/10.3390/transplantology2020021 - 11 Jun 2021

Cited by 2 | Viewed by 1742

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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