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The Journal of Heart and Lung... Jan 2021Despite the advancements in medical treatment, mechanical support, and stem cell therapy, heart transplantation remains the most effective treatment for selected... (Review)
Review
Despite the advancements in medical treatment, mechanical support, and stem cell therapy, heart transplantation remains the most effective treatment for selected patients with advanced heart failure. However, with an increase in heart failure prevalence worldwide, the gap between donor hearts and patients on the transplant waiting list keeps widening. Ex situ machine perfusion has played a key role in augmenting heart transplant activities in recent years by enabling the usage of donation after circulatory death hearts, allowing longer interval between procurement and implantation, and permitting the safe use of some extended-criteria donation after brainstem death hearts. This exciting field is at a hinge point, with 1 commercially available heart perfusion machine, which has been used in hundreds of heart transplantations, and a number of devices being tested in the pre-clinical and Phase 1 clinical trial stage. However, no consensus has been reached over the optimal preservation temperature, perfusate composition, and perfusion parameters. In addition, there is a lack of objective measurement for allograft quality and viability. This review aims to comprehensively summarize the lessons about ex situ heart perfusion as a platform to preserve, assess, and repair donor hearts, which we have learned from the pre-clinical studies and clinical applications, and explore its exciting potential of revolutionizing heart transplantation.
Topics: Heart Transplantation; Humans; Organ Preservation; Perfusion; Tissue Donors
PubMed: 33162304
DOI: 10.1016/j.healun.2020.10.004 -
Current Opinion in Organ Transplantation Jun 2016In the current era of extreme organ shortage, warm (subnormothermic and normothermic) ex-vivo liver perfusion has emerged as a novel strategy to recover marginal organs... (Review)
Review
PURPOSE OF REVIEW
In the current era of extreme organ shortage, warm (subnormothermic and normothermic) ex-vivo liver perfusion has emerged as a novel strategy to recover marginal organs and increase the organ pool. Over the last decade, significant progress in the field has taken this technology from bench to bedside. This review will cover the most relevant contributions to the field in 2015.
RECENT FINDINGS
Several groups made significant advances in warm ex-vivo liver perfusion for optimizing preservation of liver grafts. With transition to clinical use underway, significant interest has focused on exploring the safety and feasibility of the technique. Other areas of exploration included novel perfusates and rewarming strategies. This review will also summarize the most recent advances in the clinical setting.
SUMMARY
Warm ex-vivo liver perfusion has established itself as a novel approach for the preservation of liver grafts for transplantation. Although the optimal perfusion conditions and techniques have not been established, the safety of this technique has been demonstrated in preclinical and clinical studies. Thus far, most investigation has focused on the rescue of marginal grafts. However, further development in the field has the potential to yield novel graft interventions and modification.
Topics: Extracorporeal Circulation; Humans; Liver; Liver Transplantation; Organ Preservation; Perfusion
PubMed: 27093224
DOI: 10.1097/MOT.0000000000000305 -
HPB : the Official Journal of the... Nov 2017This study aimed to identify the most effective solution for in situ perfusion/preservation of the pancreas in donation after brain death donors, in addition to optimal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This study aimed to identify the most effective solution for in situ perfusion/preservation of the pancreas in donation after brain death donors, in addition to optimal in situ flush volume(s) and route(s) during pancreas procurement.
METHODS
Embase, Medline and Cochrane databases were utilized (1980-2017). Articles comparing graft outcomes between two or more different perfusion/preservation fluids (University of Wisconsin (UW), histidine-tryptophan-ketoglutarate (HTK) and/or Celsior) were compared using random effects models where appropriate.
RESULTS
Thirteen articles were included (939 transplants). Confidence in available evidence was low. A higher serum peak lipase (standardized mean difference 0.47, 95% CI 0.23-0.71, I = 0) was observed in pancreatic grafts perfused/preserved with HTK compared to UW, but there were no differences in one-month pancreas allograft survivals or early thrombotic graft loss rates. Similarly, there were no significant differences in the rates of graft pancreatitis, thrombosis and graft survival between UW and Celsior solutions, and between aortic-only and dual aorto-portal perfusion.
CONCLUSION
UW cold perfusion may reduce peak serum lipase, but no quality evidence suggested UW cold perfusion improves graft survival and reduces thrombosis rates. Further research is needed to establish longer-term graft outcomes, the comparative efficacy of Celsior, and ideal perfusion volumes.
Topics: Adult; Cold Temperature; Female; Graft Survival; Humans; Male; Organ Preservation; Organ Preservation Solutions; Pancreas Transplantation; Pancreatectomy; Perfusion; Postoperative Complications; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Young Adult
PubMed: 28844527
DOI: 10.1016/j.hpb.2017.07.012 -
Transplantation Reviews (Orlando, Fla.) Jul 2018In recent years, remarkable progress has occurred in the development of technologies to support ex situ liver perfusion. Building upon extensive preclinical studies in... (Review)
Review
In recent years, remarkable progress has occurred in the development of technologies to support ex situ liver perfusion. Building upon extensive preclinical studies in large animal models, pilot and randomized clinical trials have been initiated, and preliminary outcomes suggest more optimal protection of both standard and extended criteria liver grafts. There currently exists an incredible opportunity and need to further refine this technology, determine appropriate viability measures to predict usable liver grafts, and to explore potent protective additive strategies to further optimize the quality of extended criteria organs. These findings will have major bearing in expanding the limited liver donor pool, and may save lives where up to a quarter of listed patients die on wait-lists. Herein we offer a brief overview of the history and current status of ex situ liver perfusion, and discuss future directions that will likely have major impact on the practice of clinical liver transplantation.
Topics: Humans; Liver; Liver Transplantation; Organ Preservation; Perfusion
PubMed: 29691119
DOI: 10.1016/j.trre.2018.03.002 -
Nature Protocols Jun 2021As engineered tissues progress toward therapeutically relevant length scales and cell densities, it is critical to deliver oxygen and nutrients throughout the tissue...
As engineered tissues progress toward therapeutically relevant length scales and cell densities, it is critical to deliver oxygen and nutrients throughout the tissue volume via perfusion through vascular networks. Furthermore, seeding of endothelial cells within these networks can recapitulate the barrier function and vascular physiology of native blood vessels. In this protocol, we describe how to fabricate and assemble customizable open-source tissue perfusion chambers and catheterize tissue constructs inside them. Human endothelial cells are seeded along the lumenal surfaces of the tissue constructs, which are subsequently connected to fluid pumping equipment. The protocol is agnostic with respect to biofabrication methodology as well as cell and material composition, and thus can enable a wide variety of experimental designs. It takes ~14 h over the course of 3 d to prepare perfusion chambers and begin a perfusion experiment. We envision that this protocol will facilitate the adoption and standardization of perfusion tissue culture methods across the fields of biomaterials and tissue engineering.
Topics: Endothelial Cells; Humans; Perfusion; Tissue Engineering
PubMed: 34031610
DOI: 10.1038/s41596-021-00533-1 -
Perfuse and Reuse: A Low-Cost Three-Dimensional-Printed Perfusion Bioreactor for Tissue Engineering.Tissue Engineering. Part C, Methods Nov 2022This article describes fabrication of a customizable bioreactor, which comprises a perfusion system and coverslip-based tissue culture chamber that allow...
This article describes fabrication of a customizable bioreactor, which comprises a perfusion system and coverslip-based tissue culture chamber that allow centimeter-scale vascularized or otherwise canalized tissue constructs to be maintained in weeks long static and/or perfusion culture at an exceptionally low cost, with intermittent live imaging and media sampling capabilities. The perfusion system includes a reusable polydimethylsiloxane (PDMS) lid generated from a three-dimensional (3D)-printed poly-lactic acid (PLA) mold and several lengths of perfusion tubing. The coverslip tissue culture chamber includes PDMS components built with 3D-printed PLA molds, as well as 3D-printed PLA frames and glass coverslips that house perfusable hydrogel constructs. As proof of concept, we fabricated a vascularized hydrogel construct, which was subjected to static and perfusion tissue culture, as well as flow studies using fluorescent beads and widefield fluorescent microscopy. This system can be readily reproduced, promoting the advancement of tissue engineering and regenerative medicine research.
Topics: Tissue Engineering; Perfusion; Bioreactors; Hydrogels; Polyesters; Printing, Three-Dimensional; Tissue Scaffolds
PubMed: 36094108
DOI: 10.1089/ten.TEC.2022.0139 -
Annals of Transplantation Aug 2021A shortage of available organs for liver transplantation has led transplant surgeons and researchers to seek for innovative approaches in hepatoprotection and... (Review)
Review
A shortage of available organs for liver transplantation has led transplant surgeons and researchers to seek for innovative approaches in hepatoprotection and improvement of marginal allografts. The most exciting development in the past decade has been continuous mechanical perfusion of livers with blood or preservation solution to mitigate ischemia-reperfusion injury in contrast to the current standard of static cold storage. Two variations of machine perfusion have emerged in clinical practice. During hypothermic oxygenated perfusion the liver is perfused using a red blood cell-free perfusate at 2-10°C. In contrast, normothermic machine perfusion mimics physiologic liver perfusion using a red blood cell-based solution at 35.5-037.5°C, offering a multitude of potential advantages. Putative effects of normothermic perfusion include abrogation of hyperfibrinolysis after reperfusion and inflammation, glycogen repletion, and regeneration of adenosine triphosphate. Research in normothermic machine perfusion focuses on development of biomarkers predicting allograft quality and susceptibility to ischemia-reperfusion injury. Moreover, normothermic perfusion of marginal allografts allows for application of a variety of therapeutic interventions potentially enhancing organ quality. Both methods need to be subjected to translational investigation and evaluation in clinical trials. A clear advantage is transformation of an emergency procedure at night into a planned daytime surgery. Current clinical trials suggest that normothermic perfusion not only increases the use of hepatic allografts but is also associated with milder ischemia-reperfusion injury, resulting in a reduced risk of early allograft dysfunction and less biliary complications, including ischemic cholangiopathy, compared to static cold storage. The aim of this review is to give a concise overview of normothermic machine perfusion and its current applications, benefits, and possible advances in the future.
Topics: Aged; Biomarkers; Humans; Liver; Liver Transplantation; Organ Preservation; Perfusion; Reperfusion Injury
PubMed: 34426566
DOI: 10.12659/AOT.931664 -
International Journal of Molecular... Sep 2020Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality, and current management has a dramatic impact on healthcare resource... (Review)
Review
Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality, and current management has a dramatic impact on healthcare resource utilization. While our understanding of this disease has improved, the majority of treatment strategies remain supportive in nature and are associated with continued poor outcomes. There is a dramatic need for the development and breakthrough of new methods for the treatment of ARDS. Isolated machine lung perfusion is a promising surgical platform that has been associated with the rehabilitation of injured lungs and the induction of molecular and cellular changes in the lung, including upregulation of anti-inflammatory and regenerative pathways. Initially implemented in an ex vivo fashion to evaluate marginal donor lungs prior to transplantation, recent investigations of isolated lung perfusion have shifted in vivo and are focused on the management of ARDS. This review presents current tenants of ARDS management and isolated lung perfusion, with a focus on how ex vivo lung perfusion (EVLP) has paved the way for current investigations utilizing in vivo lung perfusion (IVLP) in the treatment of severe ARDS.
Topics: Animals; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Inflammation; Lung Injury; Perfusion; Respiratory Distress Syndrome; Tissue Donors
PubMed: 32957547
DOI: 10.3390/ijms21186820 -
Transplantation Sep 2020Machine perfusion (MP) is at the forefront of innovation in modern liver transplantation. Several approaches, mainly varying the temperature at which the graft is... (Review)
Review
Machine perfusion (MP) is at the forefront of innovation in modern liver transplantation. Several approaches, mainly varying the temperature at which the graft is perfused, have shown benefit in preclinical models and nonrandomized clinical trials. Given the recent randomized controlled trial by Nasralla et al demonstrating the efficacy of normothermic MP over static cold storage, MP is likely here to stay for the foreseeable future. We are only beginning to explore the possibilities of this technology, including the prediction of graft function and modification of suboptimal livers. This has the potential to both increase the donor pool and improve the quality of grafts provided to recipients. Beyond transplantation, there may be a role for MP in extracorporeal liver support, cancer research and therapeutics, and pharmaceutical testing. In this review, we provide the rationale and explore the relevant preclinical studies that support the use of ex situ liver perfusion for these extended applications.
Topics: Animals; Humans; Liver; Liver Transplantation; Models, Animal; Neoplasms; Organ Preservation; Perfusion; Toxicology
PubMed: 32433236
DOI: 10.1097/TP.0000000000003320 -
PloS One 2021Normothermic machine perfusion (NMP) of donor kidneys provides the opportunity for improved graft preservation and objective pre-transplant ex-vivo organ assessment....
Normothermic machine perfusion (NMP) of donor kidneys provides the opportunity for improved graft preservation and objective pre-transplant ex-vivo organ assessment. Currently, a multitude of perfusion solutions exist for renal NMP. This study aimed to evaluate four different perfusion solutions side-by-side and determine the influence of different perfusate compositions on measured renal perfusion parameters. Porcine kidneys and blood were obtained from a slaughterhouse. Kidneys underwent NMP at 37°C for 7 hours, with 4 different perfusion solutions (n = 5 per group). Group 1 consisted of red blood cells (RBCs) and a perfusion solution based on Williams' Medium E. Group 2 consisted of RBCs, albumin and a balanced electrolyte composition. Group 3 contained RBCs and a medium based on a British clinical NMP solution. Group 4 contained RBCs and a medium used in 24-hour perfusion experiments. NMP flow patterns for solutions 1 and 2 were similar, solutions 3 and 4 showed lower but more stable flow rates. Thiobarbituric acid reactive substances were significantly higher in solution 1 and 4 compared to the other groups. Levels of injury marker N-acetyl-β-D glucosaminidase were significantly lower in solution 2 in comparison with solution 3 and 4. This study illustrates that the perfusate composition during NMP significantly impacts the measured perfusion and injury parameters and thus affects the interpretation of potential viability markers. Further research is required to investigate the individual influences of principal perfusate components to determine the most optimal conditions during NMP and eventually develop universal organ assessment criteria.
Topics: Animals; Kidney; Kidney Transplantation; Organ Preservation; Perfusion; Swine
PubMed: 34003874
DOI: 10.1371/journal.pone.0251595