Dataset Information

Machine Perfusion and the Pancreas: Will It Increase the Donor Pool?

ABSTRACT: PURPOSE OF REVIEW:Pancreas transplantation enables complete patient independence from exogenous insulin administration and increases both patient survival and quality of life. Despite this, there has been a decline in pancreas transplantation for the past 20 years, influenced by changing donor demographics with more high-risk extended criteria (ECD) and donation after cardiac death (DCD) donors. This review discusses whether the advent of machine perfusion (MP), if extended to the pancreas, can increase the pool of suitable donor organs. RECENT FINDINGS:Hypothermic and normothermic MP, as forms of preservation deemed superior to cold storage for high-risk kidney and liver donor organs, have opened the avenue for translation of this work into the pancreas. Recent experimental models of porcine and human ex-vivo pancreatic MP are promising. Applications of MP to the pancreas however need refinement-focusing on perfusion protocols and viability assessment tools. Emerging research shows pancreatic MP can potentially offer superior preservation capacity, the ability to both resuscitate and manipulate organs, and assess functional and metabolic organ viability. The future of MP will lie in organ assessment and resuscitation after retrieval, where ultimately organs initially considered high risk and unsuitable for transplantation will be optimised and transformed, making them then available for clinical use, thus increasing the pool of suitably viable pancreata for transplantation.

SUBMITTER: Hamaoui K

PROVIDER: S-EPMC6620253 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Machine Perfusion and the Pancreas: Will It Increase the Donor Pool?

Hamaoui Karim K Papalois Vassilios V

Current diabetes reports 20190710 8

<h4>Purpose of review</h4>Pancreas transplantation enables complete patient independence from exogenous insulin administration and increases both patient survival and quality of life. Despite this, there has been a decline in pancreas transplantation for the past 20 years, influenced by changing donor demographics with more high-risk extended criteria (ECD) and donation after cardiac death (DCD) donors. This review discusses whether the advent of machine perfusion (MP), if extended to the pancre ...[more]

PMID: 31292740

Similar Datasets

Project description:Introduction: Ageing of the general population has led to an increase in the use of suboptimal kidneys from expanded criteria donation after brain death (ECD-DBD) and donation after circulatory death (DCD) donors. However, these kidneys have inferior graft outcomes and lower rates of immediate function. Normothermic machine perfusion (NMP) may improve outcomes of these suboptimal donor kidneys. Previous non-randomized studies have shown the safety of this technique and suggested its efficacy in improving the proportion of immediate functioning kidneys compared to static cold storage (SCS). However, its additional value to hypothermic machine perfusion (HMP), which has already been proved superior to SCS, has not yet been established. Methods and analysis: This single-center, open-label, randomized controlled trial aims to assess immediate kidney function after 120 minutes additional, end-ischemic NMP compared to HMP alone. Immediate kidney function is defined as no dialysis treatment in the first week after transplant. Eighty recipients on dialysis at the time of transplant who receive an ECD-DBD or DCD kidney graft are eligible for inclusion. In the NMP group, the donor kidney is taken of HMP upon arrival in the recipient hospital and thereafter put on NMP for 120 minutes at 37 degrees Celsius followed by transplantation. In the control group, donor kidneys stay on HMP until transplantation. The primary outcome is immediate kidney function. Ethics and dissemination: The protocol has been approved by the Medical Ethical Committee of Erasmus Medical Center (2020-0366). Results of this study will be submitted to peer-reviewed journals. Registration: registered in clinicaltrials.gov (NCT04882254). Highlights: This is the first RCT to compare additional NMP to HMP alone. Extensive sampling will offer in-depth analysis of kidney physiology during NMP. This RCT may help identify biomarkers to predict clinical outcomes during NMP. Biomarkers can help develop NMP as assessment tool for declined kidneys.

Project description:Background Normothermic machine perfusion (NMP) allows viability assessment and potential resuscitation of donor livers prior to transplantation. The immunological effect of NMP on liver allografts is undetermined, with potential implications on allograft function, rejection outcomes and overall survival. In this study we define the changes in immune profile of human livers during NMP. Methods Six human livers were placed on a NMP device. Tissue and perfusate samples were obtained during cold storage prior to perfusion and at 1, 3, and 6 hours of perfusion. Flow cytometry, immunohistochemistry, and bead-based immunoassays were used to measure leukocyte composition and cytokines in the perfusate and within the liver tissue. Mean values between baseline and time points were compared by Student’s t-test. Results Within circulating perfusate, significantly increased frequencies of CD4 T cells, B cells and eosinophils were detectable by 1 hour of NMP and continued to increase at 6 hours of perfusion. On the other hand, NK cell frequency significantly decreased by 1 hour of NMP and remained decreased for the duration of perfusion. Within the liver tissue there was significantly increased B cell frequency but decreased neutrophils detectable at 6 hours of NMP. A transient decrease in intermediate monocyte frequency was detectable in liver tissue during the middle of the perfusion run. Overall, no significant differences were detectable in tissue resident T regulatory cells during NMP. Significantly increased levels of pro-inflammatory and anti-inflammatory cytokines were seen following initiation of NMP that continued to rise throughout duration of perfusion. Conclusions Time-dependent dynamic changes are seen in individual leukocyte cell-types within both perfusate and tissue compartments of donor livers during NMP. This suggests a potential role of NMP in altering the immunogenicity of donor livers prior to transplant. These data also provide insights for future work to recondition the intrinsic immune profile of donor livers during NMP prior to transplantation.

Dataset Information

Machine Perfusion and the Pancreas: Will It Increase the Donor Pool?

Publications

Machine Perfusion and the Pancreas: Will It Increase the Donor Pool?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets