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Acta Pharmacologica Sinica May 2018Organ transplantation is the most effective therapy for patients with end-stage disease. Preservation solutions and techniques are crucial for donor organ quality, which... (Review)
Review
Organ transplantation is the most effective therapy for patients with end-stage disease. Preservation solutions and techniques are crucial for donor organ quality, which is directly related to morbidity and survival after transplantation. Currently, static cold storage (SCS) is the standard method for organ preservation. However, preservation time with SCS is limited as prolonged cold storage increases the risk of early graft dysfunction that contributes to chronic complications. Furthermore, the growing demand for the use of marginal donor organs requires methods for organ assessment and repair. Machine perfusion has resurfaced and dominates current research on organ preservation. It is credited to its dynamic nature and physiological-like environment. The development of more sophisticated machine perfusion techniques and better perfusates may lead to organ repair/reconditioning. This review describes the history of organ preservation, summarizes the progresses that has been made to date, and discusses future directions for organ preservation.
Topics: Animals; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Organ Preservation; Organ Preservation Solutions; Perfusion
PubMed: 29565040
DOI: 10.1038/aps.2017.182 -
Current Opinion in Organ Transplantation Feb 2020To summarise recently published studies of donor pretreatment and machine perfusion strategies in kidney transplantation. (Review)
Review
PURPOSE OF REVIEW
To summarise recently published studies of donor pretreatment and machine perfusion strategies in kidney transplantation.
RECENT FINDINGS
The sparsity of donor pretreatment trials has resulted in the re-analysis of already existing data, and RCTs are urgently needed to reinvigorate this aspect of donor research. Uncontrolled donation after circulatory death kidney transplantation has the highest risk of delayed graft function and graft failure, and recent studies have reported that normothermic regional perfusion improves graft function and survival in this setting. Hypothermic machine perfusion reduces delayed graft function following deceased donor kidney transplantation across donor types but unanswered questions still remain regarding its use. The use of oxygenated hypothermic machine perfusion appears to improve graft function in controlled donation after circulatory death mediated by a reduction in acute rejection. Ex-situ normothermic perfusion is emerging and while technically challenging it may facilitate the delivery of pretreatments.
SUMMARY
RCTs are urgently needed to reinvigorate research into donor pretreatment and to establish the place of specific preservation techniques in deceased donor kidney transplantation.
Topics: Humans; Organ Preservation; Organ Transplantation; Perfusion; Tissue Donors
PubMed: 31834008
DOI: 10.1097/MOT.0000000000000725 -
Current Opinion in Organ Transplantation Jun 2016The purpose of the review is to report recent human application of hypothermic machine liver perfusion, and to discuss potential protective mechanisms. (Review)
Review
PURPOSE OF THE REVIEW
The purpose of the review is to report recent human application of hypothermic machine liver perfusion, and to discuss potential protective mechanisms.
RECENT FINDINGS
Human application of hypothermic machine liver perfusion is still very limited. Currently, three transplant centers apply this novel treatment in donation after cardiac death (DCD) or donation after brain death (DBD) liver grafts. In all cases, endischemic perfusion was performed after initial cold storage for organ transport. Perfusion conditions differ slightly in terms of oxygenation (pO2 15-60 kPa), perfusion route (dual vs. portal), perfusion time (2-4 h), and perfusate.
SUMMARY
The current data support the hypothesis that applying endischemic hypothermic machine liver perfusion protects extended criteria DBD and DCD livers from initial reperfusion injury, with better graft function and less biliary complications. Hypothermic machine perfusion may therefore offer revitalization of liver grafts before implantation by a simple and practical perfusion technique with a high impact on enlarging the donor pool. Multicentric phase III randomized control trials in DBD and DCD liver transplantation have been initiated to further test this strategy, which may establish machine liver perfusion in the clinical setting.
Topics: Humans; Hypothermia, Induced; Liver Transplantation; Organ Preservation; Perfusion; Reactive Oxygen Species
PubMed: 26918882
DOI: 10.1097/MOT.0000000000000303 -
Advanced Healthcare Materials May 2021Engineering functional human tissues in vitro is currently limited by difficulty replicating the small caliber, complex connectivity, cellularity, and 3D curvature of...
Engineering functional human tissues in vitro is currently limited by difficulty replicating the small caliber, complex connectivity, cellularity, and 3D curvature of the native microvasculature. Multiphoton ablation has emerged as a promising technique for fabrication of microvascular structures with high resolution and full 3D control, but cellularization and perfusion of complex capillary-scale structures has remained challenging. Here, multiphoton ablation combined with guided endothelial cell growth from pre-formed microvessels is used to successfully create perfusable and cellularized organ-specific microvascular structures at anatomic scale within collagen hydrogels. Fabrication and perfusion of model 3D pulmonary and renal microvascular beds is demonstrated, as is replication and perfusion of a brain microvascular unit derived from in vivo data. Successful endothelialization and blood perfusion of a kidney-specific microvascular structure is achieved, using laser-guided angiogenesis. Finally, proof-of-concept hierarchical blood vessels and complex multicellular models are created, using multistep patterning with multiphoton ablation techniques. These successes open new doors for the creation of engineered tissues and organ-on-a-chip devices.
Topics: Ablation Techniques; Endothelial Cells; Humans; Microvessels; Perfusion; Tissue Engineering; Veins
PubMed: 33586357
DOI: 10.1002/adhm.202100031 -
International Journal of Medical... 2021Nowadays, liver transplantation is the most effective treatment for end-stage liver disease. However, the increasing imbalance between growing demand for liver... (Review)
Review
Nowadays, liver transplantation is the most effective treatment for end-stage liver disease. However, the increasing imbalance between growing demand for liver transplantation and the shortage of donor pool restricts the development of liver transplantation. How to expand the donor pool is a significant problem to be solved clinically. Many doctors have devoted themselves to marginal grafting, which introduces livers with barely passable quality but a high risk of transplant failure into the donor pool. However, existing common methods of preserving marginal grafts lead to both high risk of postoperative complications and high mortality. The application of machine perfusion allows surgeons to make marginal livers meet the standard criteria for transplant, which shows promising prospect in preserving and repairing donor livers and improving ischemia reperfusion injury. This review summarizes the progress of recent researches on hepatic machine perfusion.
Topics: Humans; Liver Transplantation; Organ Preservation; Perfusion; Reperfusion Injury; Tissue and Organ Harvesting
PubMed: 33850464
DOI: 10.7150/ijms.56139 -
International Journal of Molecular... Jun 2023Building the inner layer of our blood vessels, the endothelium forms an important line communicating with deeper parenchymal cells in our organs. Previously considered... (Review)
Review
Building the inner layer of our blood vessels, the endothelium forms an important line communicating with deeper parenchymal cells in our organs. Previously considered passive, endothelial cells are increasingly recognized as key players in intercellular crosstalk, vascular homeostasis, and blood fluidity. Comparable to other cells, their metabolic function strongly depends on mitochondrial health, and the response to flow changes observed in endothelial cells is linked to their mitochondrial metabolism. Despite the direct impact of new dynamic preservation concepts in organ transplantation, the impact of different perfusion conditions on sinusoidal endothelial cells is not yet explored well enough. This article therefore describes the key role of liver sinusoidal endothelial cells (LSECs) together with their mitochondrial function in the context of liver transplantation. The currently available ex situ machine perfusion strategies are described with their effect on LSEC health. Specific perfusion conditions, including perfusion pressure, duration, and perfusate oxygenation are critically discussed considering the metabolic function and integrity of liver endothelial cells and their mitochondria.
Topics: Liver Transplantation; Endothelial Cells; Liver; Hepatocytes; Mitochondria; Perfusion; Organ Preservation
PubMed: 37373238
DOI: 10.3390/ijms241210091 -
Nature Communications Aug 2023Current machine perfusion technology permits livers to be preserved ex situ for short periods to assess viability prior to transplant. Long-term normothermic perfusion...
Current machine perfusion technology permits livers to be preserved ex situ for short periods to assess viability prior to transplant. Long-term normothermic perfusion of livers is an emerging field with tremendous potential for the assessment, recovery, and modification of organs. In this study, we aimed to develop a long-term model of ex situ perfusion including a surgical split and simultaneous perfusion of both partial organs. Human livers declined for transplantation were perfused using a red blood cell-based perfusate under normothermic conditions (36 °C) and then split and simultaneously perfused on separate machines. Ten human livers were split, resulting in 20 partial livers. The median ex situ viability was 125 h, and the median ex situ survival was 165 h. Long-term survival was demonstrated by lactate clearance, bile production, Factor-V production, and storage of adenosine triphosphate. Here, we report the long-term ex situ perfusion of human livers and demonstrate the ability to split and perfuse these organs using a standardised protocol.
Topics: Humans; Liver Transplantation; Liver; Perfusion; Bile; Preservation, Biological
PubMed: 37553343
DOI: 10.1038/s41467-023-40154-8 -
Nature Medicine Jun 2023Kidney transplantation is the optimal treatment for end-stage renal disease, but it is still severely limited by a lack of suitable organ donors. Kidneys from donation... (Randomized Controlled Trial)
Randomized Controlled Trial
Kidney transplantation is the optimal treatment for end-stage renal disease, but it is still severely limited by a lack of suitable organ donors. Kidneys from donation after circulatory death (DCD) donors have been used to increase transplant rates, but these organs are susceptible to cold ischemic injury in the storage period before transplantation, the clinical consequence of which is high rates of delayed graft function (DGF). Normothermic machine perfusion (NMP) is an emerging technique that circulates a warmed, oxygenated red-cell-based perfusate through the kidney to maintain near-physiological conditions. We conducted a randomized controlled trial to compare the outcome of DCD kidney transplants after conventional static cold storage (SCS) alone or SCS plus 1-h NMP. A total of 338 kidneys were randomly allocated to SCS (n = 168) or NMP (n = 170), and 277 kidneys were included in the final intention-to-treat analysis. The primary endpoint was DGF, defined as the requirement for dialysis in the first 7 d after transplant. The rate of DGF was 82 of 135 (60.7%) in NMP kidneys versus 83 of 142 (58.5%) in SCS kidneys (adjusted odds ratio (95% confidence interval) 1.13 (0.69-1.84); P = 0.624). NMP was not associated with any increase in transplant thrombosis, infectious complications or any other adverse events. A 1-h period of NMP at the end of SCS did not reduce the rate of DGF in DCD kidneys. NMP was demonstrated to be feasible, safe and suitable for clinical application. Trial registration number: ISRCTN15821205 .
Topics: Humans; Kidney Transplantation; Organ Preservation; Kidney; Perfusion; Tissue Donors
PubMed: 37231075
DOI: 10.1038/s41591-023-02376-7 -
General Thoracic and Cardiovascular... Apr 2021Lung transplantation is an established life-saving intervention for patients with end-stage lung diseases. The success of lung transplantation mainly depends on the... (Review)
Review
Lung transplantation is an established life-saving intervention for patients with end-stage lung diseases. The success of lung transplantation mainly depends on the quality and function of the implanted donor lungs, which are frequently subject to brain-death-induced lung injuries and intensive care unit (ICU)-related complications before transplantation. Recent innovations, particularly the development of ex vivo lung perfusion (EVLP), in which donor lungs are ventilated and perfused under normothermic conditions outside the body, have allowed clinicians to more accurately assess the donor lung function prior to transplantation. Therefore, EVLP has been successfully translated into clinical practice with the expansion of the donor lung pool, leading to favorable post-transplant outcomes in a growing number of transplant centers worldwide. The EVLP system and techniques, following the Toronto protocol, have recently been applied for the assessment of extended criteria brain-death donors in clinical lung transplantation in Japan. The advancement of EVLP from organ assessment to organ treatment will be the next challenging stage not only to expand donor lung pool, but also to improve graft survival and long-term outcomes after transplantation.
Topics: Extracorporeal Circulation; Humans; Japan; Lung; Lung Transplantation; Organ Preservation; Perfusion; Tissue Donors
PubMed: 33683575
DOI: 10.1007/s11748-021-01609-1 -
International Angiology : a Journal of... Jun 2023To perform a scoping review analyzing the current evidence reporting on acute kidney injury (AKI) after elective open surgery (OS) of complex abdominal aortic aneurysms... (Review)
Review
INTRODUCTION
To perform a scoping review analyzing the current evidence reporting on acute kidney injury (AKI) after elective open surgery (OS) of complex abdominal aortic aneurysms (c-AAAs) and evaluate the impact of renal perfusion, and the different types of solutions on renal morbidity.
EVIDENCE ACQUISITION
Research questions were defined, and a literature search was performed following the PRISMA guidelines for scoping reviews. Multicenter, single-center observational studies were considered eligible. No abstracts only and unpublished literature were included.
EVIDENCE SYNTHESIS
Two hundred and fifty studies were screened, 20 studies met screening criteria and were included, reporting 1552 patients treated for c-AAAs. The majority did not receive renal perfusion and the others received different types of renal perfusions. Acute kidney injury is a common complication after c-AAAs OS, with an incidence up to 32.5%. Heterogeneity in AKI classifications reduce the ability to compare outcomes after perfusion and nonperfusion strategies. Pre-existing CKD, ischemic injury due to suprarenal aortic clamping are major determinants of AKI after aortic surgery. Most papers reported chronic kidney disease (CKD) at admission. Another debated topic is the indication for renal perfusion during c-AAAs OS. Controversial results for cold renal perfusion have been found.
CONCLUSIONS
In the context of c-AAAs, this review identified the need to standardize the definition of AKI to reduce reporting bias. Besides this, it showed the need to assess the indication for renal perfusion and the type of perfusion solution to be used.
Topics: Humans; Acute Kidney Injury; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Multicenter Studies as Topic; Perfusion; Renal Insufficiency, Chronic
PubMed: 37222507
DOI: 10.23736/S0392-9590.23.05021-6