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Ex vivo liver perfusion

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https://www.readbyqxmd.com/read/28266040/ex-vivo-porcine-organ-perfusion-models-as-a-suitable-platform-for-translational-transplant-research
#1
Rohan Kumar, Wen Yuan Chung, Ashley Robert Dennison, Giuseppe Garcea
In transplantation surgery, extending the criteria for organ donation to include organs that may have otherwise been previously discarded has provided the impetus to improve organ preservation. The traditional method of cold static storage (CS) has been tried and tested and is suitable for organs meeting standard criteria donation. Ex vivo machine perfusion is, however, associated with evidence suggesting that it may be better than CS alone and may allow for organ donation criteria to be extended. Much of our knowledge of organ preservation is derived from animal studies...
March 6, 2017: Artificial Organs
https://www.readbyqxmd.com/read/28241986/short-fasting-does-not-protect-perfused-ex%C3%A2-vivo-rat-liver-against-ischemia-reperfusion-on-the-importance-of-a-minimal-cell-energy-charge
#2
Bérengère Papegay, Michaela Stadler, Vincent Nuyens, Véronique Kruys, Jean G Boogaerts, Joseph Vamecq
OBJECTIVE: Dietary restriction or reduced food intake was supported to protect against renal and hepatic ischemic injury. In this vein, short fasting was recently shown to protect in situ rat liver against ischemia-reperfusion. Here, perfused ex vivo instead of in situ livers were exposed to ischemia-reperfusion to study the impact of disconnecting liver from extrahepatic supply in energetic substrates on the protection given by short-term fasting. METHODS: Perfused ex vivo livers using short (18 h) fasted compared with fed rats were submitted to ischemia-reperfusion and studied for release of cytolysis markers in the perfusate...
March 2017: Nutrition
https://www.readbyqxmd.com/read/28240817/liver-ex-vivo-machine-perfusion-preservation-a-review-of-the-methodology-and-results-of-large-animal-studies-and-clinical-trials
#3
REVIEW
Hazel Marecki, Adel Bozorgzadeh, Robert Porte, Henri Leuvenink, Korkut Uygun, Paulo Martins
Ex-vivo machine perfusion is a promising way to better preserve livers prior to transplantation. Currently, no methodology has verified benefit over simple cold storage. Before becoming clinically feasible, machine perfusion requires validation in models that reliably predict human performance. Such a model has been found in porcine liver, who's physiological, anatomical, and immunological characteristics closely resemble the human liver. Since the 1930s, researchers have explored machine perfusion as preservation, but only recently have clinical trials been performed...
February 27, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28104168/meld-and-child-pugh-scores-are-related-to-immune-status-of-intrahepatic-natural-killer-cells-in-liver-transplant-candidates
#4
N Tanimine, Y Tanaka, T Abe, J Piao, K Ishiyama, T Kobayashi, K Ide, M Ohira, H Tahara, S Shimizu, Y Saeki, H Sakai, T Yano, H Ohdan
BACKGROUND: The role and phenotypic alterations of intrahepatic natural killer (NK) cells in liver disease were investigated. Although intrahepatic NK cells reportedly functionally deteriorate in the fibrotic liver, it remains unclear how the clinical severity of liver disease affects intrahepatic NK cells in patients with advanced liver failure. METHODS: We analyzed the phenotypic properties of intrahepatic NK cells by using mononuclear cells extracted from ex vivo liver perfusate effluents from patients who underwent liver transplantation...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/27992805/selective-ex%C3%A2-vivo-photothermal-nano-therapy-of-solid-liver-tumors-mediated-by-albumin-conjugated-gold-nanoparticles
#5
Lucian Mocan, Cristian Matea, Flaviu A Tabaran, Ofelia Mosteanu, Teodora Pop, Cosmin Puia, Lucia Agoston-Coldea, Gabriela Zaharie, Teodora Mocan, Anca Dana Buzoianu, Cornel Iancu
We have used albumin (BSA) bound to gold nanoparticles (GNPs) as active vectors to target liver cells. Our incentive to develop an original model of living liver cancer sprang from the ethical drawbacks that hindered the assessment of the selective character and the therapeutic capacity of these nano-biosystems in cancer patients. Ex vivo-perfused liver specimens were obtained from hepatocellular carcinoma patients similarly to the surgical technique of transplantation. Albumin bound to GNPs was inoculated intra-arterially onto the resulting specimen and determined the specific delivery of the nano-bioconjugate into the malignant tissue by means of the capillary bed...
March 2017: Biomaterials
https://www.readbyqxmd.com/read/27957815/evolution-of-graft-morphology-and-function-after-recellularization-of-decellularized-rat-livers
#6
Antje Butter, Khalid Aliyev, Karl-Herbert Hillebrandt, Nathanael Raschzok, Martin Kluge, Nicolai Seiffert, Peter Tang, Hendrik Napierala, Muhammad Imtiaz Ashraf, Anja Reutzel-Selke, Andreas Andreou, Johann Pratschke, Igor Maximilian Sauer, Benjamin Struecker
Decellularization of livers is a well-established procedure. Data on different reseeding techniques or the functional evolution and re-organization processes of repopulated grafts remains limited. We established a proprietary, customized bioreactor to repopulate decellularized rat livers (n = 21) with primary rat hepatocytes (150 x 10(6) cells) via the hepatic artery and to subsequently evaluate graft morphology and function during seven days of ex vivo perfusion. Grafts were analyzed at 1 h, 6 h, 12 h, 24 h, 3d, 5d and 7d after recellularization (all n = 3) by immuno-histologic evaluation, hepatocyte-related enzyme (AST, ALT, LDH) and albumin measurement in the perfusate...
December 13, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27941437/activation-of-fibrinolysis-but-not-coagulation-during-end-ischemic-ex-situ-normothermic-machine-perfusion-of-human-donor-livers
#7
Shanice A Karangwa, Laura C Burlage, Jelle Adelmeijer, Negin Karimian, Andrie C Westerkamp, Alix P Matton, Rianne van Rijn, Janneke Wiersema-Buist, Micheal E Sutton, Sanna Op den Dries, Ton Lisman, Robert J Porte
BACKGROUND: Ex situ normothermic machine perfusion (NMP) can be performed after traditional static cold preservation to assess graft function and viability before transplantation. It is unknown whether this results in activation of coagulation and fibrinolysis, as may occur upon graft reperfusion in vivo. METHODS: Twelve donor livers declined for transplantation underwent 6 hours of end-ischemic NMP using a heparinized plasma-based perfusion fluid. Concentration of prothrombin fragment F1 + 2 (marker of coagulation activation), D-dimer, plasmin-antiplasmin complex, tissue plasminogen activator and plasminogen activator inhibitor-1 (markers for fibrinolysis) and alanine aminotransferase (ALT) (marker of ischemia-reperfusion [I/R] injury) were measured in perfusion fluid at regular intervals...
February 2017: Transplantation
https://www.readbyqxmd.com/read/27867357/machine-perfusion-of-porcine-livers-with-oxygen-carrying-solution-results-in-reprogramming-of-dynamic-inflammation-networks
#8
David Sadowsky, Ruben Zamora, Derek Barclay, Jinling Yin, Paulo Fontes, Yoram Vodovotz
Background:Ex vivo machine perfusion (MP) can better preserve organs for transplantation. We have recently reported on the first application of an MP protocol in which liver allografts were fully oxygenated, under dual pressures and subnormothermic conditions, with a new hemoglobin-based oxygen carrier (HBOC) solution specifically developed for ex vivo utilization. In those studies, MP improved organ function post-operatively and reduced inflammation in porcine livers. Herein, we sought to refine our knowledge regarding the impact of MP by defining dynamic networks of inflammation in both tissue and perfusate...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27860296/impact-of-subnormothermic-machine-perfusion-preservation-in-severely-steatotic-rat-livers-a-detailed-assessment-in-an-isolated-setting
#9
Y Okamura, K Hata, H Tanaka, H Hirao, T Kubota, O Inamoto, S Kageyama, I Tamaki, N Yermek, J Yoshikawa, S Uemoto
The current drastic shortage of donor organs has led to acceptance of extended-criteria donors for transplantation, despite higher risk of primary nonfunction. Here, we report the impact of subnormothermic machine perfusion (SMP) preservation on the protection of >50% macrosteatotic livers. Dietary hepatic steatosis was induced in Wistar rats via 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. This protocol induces 50-60% macrovesicular steatosis, which should be discarded when preserved via cold storage (CS)...
November 10, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27805597/study-of-viral-vectors-in-a-three-dimensional-liver-model-repopulated-with-the-human-hepatocellular-carcinoma-cell-line-hepg2
#10
Thomas Hiller, Viola Röhrs, Eva-Maria Dehne, Anke Wagner, Henry Fechner, Roland Lauster, Jens Kurreck
This protocol describes the generation of a three-dimensional (3D) ex vivo liver model and its application to the study and development of viral vector systems. The model is obtained by repopulating the extracellular matrix of a decellularized rat liver with a human hepatocyte cell line. The model permits studies in a vascularized 3D cell system, replacing potentially harmful experiments with living animals. Another advantage is the humanized nature of the model, which is closer to human physiology than animal models...
October 24, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27805315/inducing-hepatitis-c-virus-resistance-after-pig-liver-transplantation-a-proof-of-concept-of-liver-graft-modification-using-warm-ex-vivo-perfusion
#11
N Goldaracena, V N Spetzler, J Echeverri, J M Kaths, V Cherepanov, R Persson, M G Hodges, H L A Janssen, N Selzner, D R Grant, J J Feld, M Selzner
Normothermic ex vivo liver perfusion (NEVLP) offers the potential to optimize graft function prior to liver transplantation (LT). Hepatitis C virus (HCV) is dependent on the presence of miRNA(microRNA)-122. Miravirsen, a locked-nucleic acid oligonucleotide, sequesters miR-122 and inhibits HCV replication. The aim of this study was to assess the efficacy of delivering miravirsen during NEVLP to inhibit miR-122 function in a pig LT model. Pig livers were treated with miravirsen during NEVLP or cold storage (CS)...
November 2, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27771093/normothermic-ex-vivo-liver-perfusion-from-donors-after-type-2-cardiac-arrest
#12
Mihai-Calin Pavel, Constantino Fondevila Campo, Victor Molina Santos, Alba Diaz Lorca, Juan Carlos Garcia-Valdecasas Salgado
No abstract text is available yet for this article.
October 19, 2016: Cirugía Española
https://www.readbyqxmd.com/read/27768066/long-term-high-resolution-intravital-microscopy-in-the-lung-with-a-vacuum-stabilized-imaging-window
#13
Carolina Rodriguez-Tirado, Takanori Kitamura, Yu Kato, Jeffery W Pollard, John S Condeelis, David Entenberg
Metastasis to secondary sites such as the lung, liver and bone is a traumatic event with a mortality rate of approximately 90% (1). Of these sites, the lung is the most difficult to assess using intravital optical imaging due to its enclosed position within the body, delicate nature and vital role in sustaining proper physiology. While clinical modalities (positron emission tomography (PET), magnetic resonance imaging (MRI) and computed tomography (CT)) are capable of providing noninvasive images of this tissue, they lack the resolution necessary to visualize the earliest seeding events, with a single pixel consisting of nearly a thousand cells...
October 6, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27732765/graft-versus-host-disease-following-liver-transplantation-development-of-a-high-incidence-rat-model-and-a-selective-prevention-method
#14
E Yu, H Ueta, H Kimura, Y Kitazawa, Y Sawanobori, K Matsuno
Graft-versus-host disease (GvHD) following liver transplantation (LT) is a rare but serious complication with no presently available animal model and no preventive measures. To develop a rat model of GvHD after LT (LT-GvHD), we preconditioned hosts with sublethal irradiation plus reduction of natural killer (NK) cells with anti-CD8α mAb treatment, which invariably resulted in acute LT-GvHD. Compared with those in the peripheral counterpart, graft CD4(+) CD25(-) passenger T cells showed lower alloreactivities in mixed leukocyte culture...
October 12, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27695056/the-fatty-acid-synthase-inhibitor-platensimycin-improves-insulin-resistance-without-inducing-liver-steatosis-in-mice-and-monkeys
#15
Sheo B Singh, Ling Kang, Andrea R Nawrocki, Dan Zhou, Margaret Wu, Stephen Previs, Corey Miller, Haiying Liu, Catherine D G Hines, Maria Madeira, Jin Cao, Kithsiri Herath, Liangsu Wang, David E Kelley, Cai Li, Hong-Ping Guan
OBJECTIVES: Platensimycin (PTM) is a natural antibiotic produced by Streptomyces platensis that selectively inhibits bacterial and mammalian fatty acid synthase (FAS) without affecting synthesis of other lipids. Recently, we reported that oral administration of PTM in mouse models (db/db and db/+) with high de novo lipogenesis (DNL) tone inhibited DNL and enhanced glucose oxidation, which in turn led to net reduction of liver triglycerides (TG), reduced ambient glucose, and improved insulin sensitivity...
2016: PloS One
https://www.readbyqxmd.com/read/27670067/effects-of-nitrite-addition-to-igl-1-solution-on-rat-liver-preservation
#16
Amani Cherif-Sayadi, Kaouther Hadj Ayed-Tka, Mohamed Bejaoui, Neyla Ben Gdara, Mohamed Amine Zaouali, Hassen Ben Abdennebi
BACKGROUND The ability of nitrite to provide protection following ischemia/reperfusion (I/R) has been demonstrated, but its mechanism is still poorly understood. This study aimed to determine the optimal nitrite concentration to add into Institut Georges Lopez (IGL-1) storage solution and to assess its effect on antioxidant enzymes and autophagy. MATERIAL AND METHODS Livers from Sprague-Dawley rats were conserved in IGL-1 for 24 hours at 4°C or in IGL-1 enriched with nitrite at 50, 500 and 1,000 nM, respectively, before being perfused ex-vivo at 37 °C for 120 minutes...
2016: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/27646847/synthesis-and-evaluation-of-18-f-labeled-pyridaben-analogues-for-myocardial-perfusion-imaging-in-mice-rats-and-chinese-mini-swine
#17
Tiantian Mou, Zuoquan Zhao, Linyi You, Yesen Li, Qian Wang, Wei Fang, Jie Lu, Cheng Peng, Xianzhong Zhang
This study reports three novel (18)F-labeled pyridaben analogues for potential myocardial perfusion imaging (MPI). Three precursors and the corresponding nonradioactive compounds were synthesized and characterized. The radiolabeled tracers were obtained by substituting tosyl with (18)F. The total radiosynthesis time of these tracers was 70-90 min. Typical decay-corrected radiochemical yields were 47-58%, with high radiochemical purities (>98%). Tracers were evaluated as MPI agents in vitro, ex vivo and in vivo...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27639262/preliminary-single-center-canadian-experience-of-human-normothermic-ex-vivo-liver-perfusion-results-of-a-clinical-trial
#18
M Bral, B Gala-Lopez, D Bigam, N Kneteman, A Malcolm, S Livingstone, A Andres, J Emamaullee, L Russell, C Coussios, L J West, P J Friend, A M J Shapiro
After extensive experimentation, outcomes of a first clinical normothermic machine perfusion (NMP) liver trial in the United Kingdom demonstrated feasibility and clear safety, with improved liver function compared with standard static cold storage (SCS). We present a preliminary single-center North American experience using identical NMP technology. Ten donor liver grafts were procured, four (40%) from donation after circulatory death (DCD), of which nine were transplanted. One liver did not proceed because of a technical failure with portal cannulation and was discarded...
September 17, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27556578/anti-inflammatory-signaling-during-ex-vivo-liver-perfusion-improves-the-preservation-of-pig-liver-grafts-before-transplantation
#19
Nicolas Goldaracena, Juan Echeverri, Vinzent N Spetzler, Johan M Kaths, Andrew S Barbas, Kristine S Louis, Oyedele A Adeyi, David R Grant, Nazia Selzner, Markus Selzner
Normothermic ex vivo liver perfusion (NEVLP) improves graft preservation by avoiding cold ischemia injury. We investigated whether the protective effects of NEVLP can be further improved by applying strategies targeted on reducing the activation of proinflammatory cytokines during perfusion. Livers retrieved under heart-beating conditions were perfused for 4 hours. Following the preservation period, a pig liver transplantation was performed. In group 1 (n = 5), anti-inflammatory strategies (alprostadil, n-acetylcysteine, carbon monoxide, sevoflurane, and subnormothermic temperature [33°C]) were applied...
November 2016: Liver Transplantation
https://www.readbyqxmd.com/read/27554068/microvascular-injury-and-perfusion-changes-induced-by-ultrasound-and-microbubbles-in-a-machine-perfused-pig-liver
#20
Christina P Keravnou, Ine De Cock, Ine Lentacker, Maria-Louisa Izamis, Michalakis A Averkiou
Localized drug delivery and uptake can benefit from the combined action of ultrasound and microbubbles at a specific site. Some of the possible mechanisms suggested are vessel poration and/or cell poration, but the exact acoustic parameters that trigger those phenomena remain unknown. Ex vivo machine perfusion of human-sized organs is a technique that provides an ideal environment for pre-clinical investigations with high physiologic relevance not possible with in vitro experiments. In this work, ex vivo machine-perfused pig livers were combined with an image-guided therapy system to investigate microvascular flow changes caused by the interaction of ultrasound-driven microbubbles with the vasculature...
November 2016: Ultrasound in Medicine & Biology
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