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Pig liver transplant

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https://www.readbyqxmd.com/read/29705279/effects-of-subnormothermic-perfusion-before-transplantation-for-liver-grafts-from-donation-after-cardiac-death-a-simplified-dripping-perfusion-method-in-pigs
#1
Y Kakizaki, S Miyagi, K Shimizu, H Kumata, M Matsumura, Y Miyazaki, K Fukuoka, S S Uematsu, K Tokodai, Y Hara, C Nakanishi, M Unno, T Kamei, M Goto
BACKGROUND: Liver transplantation from donors after cardiac death (DCD) provides a solution to the donor shortage. However, DCD liver grafts are associated with a high incidence of primary graft nonfunction. We investigated the effectiveness of subnormothermic porcine liver perfusion, before transplantation from DCD, on graft viability. METHODS: Landrace pigs (25-30 kg) were randomly allocated to 3 groups (5 per group): heart-beating (HB) graft, transplanted after a 4-hour period of cold storage (CS); DCD graft, retrieved 20 minutes after apnea-induced cardiac arrest (respiratory withdrawal) and transplanted after a 4-hour period of CS; and subnormothermic ex vivo liver perfusion (SELP) graft, retrieved in the same manner as the DCD graft but perfused with a subnormothermic oxygenated Krebs-Henseleit buffer (21-25°C, 10-15 cm H2 O) for 30 minutes in a simplified dripping manner, without a machine perfusion system, after the 4-hour period of CS, and subsequently transplanted...
April 25, 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29602096/clinical-burden-of-hepatitis-e-virus-infection-in-a-tertiary-care-center-in-flanders-belgium
#2
Lien Cattoir, Frederik Van Hoecke, Tom Van Maerken, Eveline Nys, Inge Ryckaert, Matthias De Boulle, Anja Geerts, Xavier Verhelst, Isabelle Colle, Veronik Hutse, Vanessa Suin, Magali Wautier, Steven Van Gucht, Hans Van Vlierberghe, Elizaveta Padalko
BACKGROUND: Hepatitis E virus (HEV) infection is increasingly recognized as a cause of hepatitis in developed countries. A high HEV IgG seroprevalence in humans and pigs is reported as well as sporadic clinical cases of autochtonous HEV but there are currently no data available on the clinical burden of HEV in Belgium. OBJECTIVES: The objective of the current study was to evaluate the actual clinical burden of HEV infections in our tertiary care center in Flanders, Belgium...
March 19, 2018: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/29589577/hepatitis-e-virus-hev-in-scotland-evidence-of-recent-increase-in-viral-circulation-in-humans
#3
Katrina Thom, Pamela Gilhooly, Karen McGowan, Kristen Malloy, Lisa M Jarvis, Claire Crossan, Linda Scobie, Oliver Blatchford, Alison Smith-Palmer, Mhairi C Donnelly, Janice S Davidson, Ingolfur Johannessen, Kenneth J Simpson, Harry R Dalton, Juraj Petrik
BackgroundPrevious studies showed low levels of circulating hepatitis E virus (HEV) in Scotland. We aimed to reassess current Scottish HEV epidemiology. Methods: Blood donor samples from five Scottish blood centres, the minipools for routine HEV screening and liver transplant recipients were tested for HEV antibodies and RNA to determine seroprevalence and viraemia. Blood donor data were compared with results from previous studies covering 2004-08. Notified laboratory-confirmed hepatitis E cases (2009-16) were extracted from national surveillance data...
March 2018: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/29577046/beneficial-effects-of-human-mesenchymal-stromal-cells-on-porcine-hepatocyte-viability-and-albumin-secretion
#4
Elisa Montanari, Joel Pimenta, Luca Szabó, François Noverraz, Solène Passemard, Raphael P H Meier, Jeremy Meyer, Jonathan Sidibe, Aurelien Thomas, Henk-Jan Schuurman, Sandrine Gerber-Lemaire, Carmen Gonelle-Gispert, Leo H Buhler
Porcine hepatocytes transplanted during acute liver failure might support metabolic functions until the diseased liver recovers its function. Here, we isolated high numbers of viable pig hepatocytes and evaluated hepatocyte functionality after encapsulation. We further investigated whether coculture and coencapsulation of hepatocytes with human multipotent mesenchymal stromal cells (MSC) are beneficial on hepatocyte function. Livers from 10 kg pigs ( n = 9) were harvested, and hepatocytes were isolated from liver suspensions for microencapsulation using alginate and poly(ethylene-glycol)- (PEG-) grafted alginate hydrogels, either alone or in combination with MSC...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29567935/normothermic-machine-perfusion-versus-cold-storage-of-liver-in-pig-model-a-meta-analysis
#5
Shiqi Bian, Zhijun Zhu, Liying Sun, Lin Wei, Wei Qu, Zhigui Zeng, Ying Liu
BACKGROUND Normothermic machine perfusion (NMP) is a novel strategy used for organ preservation. We aimed to determine the overall efficacy of NMP for liver preservation versus traditional static cold storage (CS). MATERIAL AND METHODS We performed a meta-analysis of the literature to evaluate the efficacy of NMP in experimental pig models of liver preservation. We use the standardized mean difference and 95% confidence intervals (CI) to calculate statistics and used the random effects model for the combined analysis of the results...
March 23, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/29538262/overcoming-coagulation-dysregulation-in-pig-solid-organ-transplantation-in-nonhuman-primates-recent-progress
#6
Liaoran Wang, David K C Cooper, Lars Burdorf, Yi Wang, Hayato Iwase
There has recently been considerable progress in the results of pig organ transplantation in nonhuman primates (NHPs), largely associated with the availability of (i) pigs genetically-engineered to overcome coagulation dysregulation, and (ii) novel immunosuppressive agents. The barriers of thrombotic microangiopathy and/or consumptive coagulation were believed to be associated with (i) activation of the graft vascular endothelial cells (VECs) by a low level of anti-pig antibody binding and/or complement deposition and/or innate immune cell activity, and (ii) molecular incompatibilities between the NHP and pig coagulation-anticoagulation systems...
March 10, 2018: Transplantation
https://www.readbyqxmd.com/read/29516261/therapeutic-potential-of-bama-miniature-pig-adipose-stem-cells-induced-hepatocytes-in-a-mouse-model-with-acute-liver-failure
#7
Shuang Zhang, Zhiqiang Zhu, Yufeng Wang, Shi Liu, Chenqiong Zhao, Weijun Guan, Yuhua Zhao
The role of mesenchymal stem cells (MSCs) in cellular therapy is well recognized in this work. MSCs have advantages of high proliferation, clone formation, multi-lineage differentiation and immunosuppression. Furthermore, adipose-resident MSCs (ADSCs) are extensively employed due to its advantages of abundant source, low cost and simple operation. Many researchers have emphasized the role of adipose-resident MSCs in the development of therapies for liver injury, but few attentions were paid on the use of induced functional hepatocytes...
March 7, 2018: Cytotechnology
https://www.readbyqxmd.com/read/29470145/portal-vein-stenosis-preconditioning-of-living-donor-liver-in-swine-early-mechanisms-of-liver-regeneration-and-gain-of-hepatic-functional-mass
#8
Pauline Brige, Geraldine Hery, Anais Palen, Théophile Guilbaud, Christophe Buffat, Anais Moyon, Jean Hardwigsen, Eric Guedj, Benjamin Guillet, Vincent Vidal, Guillaume Gorincour, Sophie Chopinet, Emilie Gregoire
In order to reduce the morbidity and mortality risk for the donor in living donor liver transplantation (LDLT), we previously identified 20% left portal vein (LPV) stenosis as the effective preconditioning to induce cell proliferation in the contralateral lobe without the downstream ipsilateral atrophy. We report, here, the pathways involved in the first hours after the preconditioning and investigate the changes in liver volume and function. Fourteen pigs entered this study. Five of them were used to study the genetic, cellular and molecular mechanisms set up in the early hours after the establishment of our preconditioning...
February 22, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29351369/heparin-but-not-tissue-plasminogen-activator-improves-outcomes-in-donation-after-circulatory-death-liver-transplantation-in-a-porcine-model
#9
Amelia J Hessheimer, Marina Vendrell, Javier Muñoz, Ángel Ruíz, Alba Díaz, Luís Flores Sigüenza, Jorge Rodríguez Lanzilotta, Eduardo Delgado Oliver, Jose Fuster, Miquel Navasa, Juan Carlos García-Valdecasas, Pilar Taurá, Constantino Fondevila
Ischemic-type biliary lesions (ITBLs) arise most frequently after donation after circulatory death (DCD) liver transplantation and result in high morbidity and graft loss. Many DCD grafts are discarded out of fear for this complication. In theory, microvascular thrombi deposited during donor warm ischemia might be implicated in ITBL pathogenesis. Herein, we aim to evaluate the effects of the administration of either heparin or the fibrinolytic drug tissue plasminogen activator (TPA) as means to improve DCD liver graft quality and potentially avoid ITBL...
January 19, 2018: Liver Transplantation
https://www.readbyqxmd.com/read/29316214/retracted-normothermic-machine-perfusion-protects-against-liver-ischemic-reperfusion-injury-during-reduced-size-liver-transplantation-in-pigs
#10
Zhi-Bin Zhang, Lei Liu, Wei Gao, Yuan Shi, Ning Ma, Zhong-Yang Shen
No abstract text is available yet for this article.
January 5, 2018: Liver Transplantation
https://www.readbyqxmd.com/read/29210476/delayed-revascularization-of-islets-after-transplantation-by-il-6-blockade-in-pig-to-non-human-primate-islet-xenotransplantation-model
#11
Byoung-Hoon Min, Jun-Seop Shin, Jong-Min Kim, Seong-Jun Kang, Hyun-Je Kim, Il-Hee Yoon, Su-Kyoung Park, Ji-Won Choi, Min-Suk Lee, Chung-Gyu Park
BACKGROUND: Pancreatic islet transplantation is currently proven as a promising treatment for type 1 diabetes patients with labile glycemic control and severe hypoglycemia unawareness. Upon islet transplantation, revascularization is essential for proper functioning of the transplanted islets. As IL-6 is important for endothelial cell survival and systemic inflammation related to xenograft, the effect of IL-6 receptor antagonist, tocilizumab, on revascularization of the transplanted islets was examined in pig to non-human primate islet xenotransplantation model...
January 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29192575/-current-dilemmas-on-the-transmission-of-hepatitis-e-virus
#12
E de Weerd-de Jong, A M Peters, J C Rahamat-Langendoen, N M A Blijlevens
Immunocompromised patients are especially at risk for developing chronic hepatitis E virus (HEV) infection, which may result in progressive liver disease and cirrhosis. In addition, treatment of chronic HEV infection in these patients often includes dose reduction of immunosuppressive therapy and this may lead to severe flare-ups of the underlying condition or even rejection of transplant material. Therefore prevention of HEV transmission is being more and more recognised as an essential step to stop increasing HEV seroprevalence...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/29189484/comparison-of-bq123-epoprostenol-and-verapamil-as-vasodilators-during-normothermic-ex-vivo-liver-machine-perfusion
#13
Juan Echeverri, Nicolas Goldaracena, Johan Moritz Kaths, Ivan Linares, Roizar Roizales, Dagmar Kollmann, Matyas Hamar, Peter Urbanellis, Sujani Ganesh, Oyedele A Adeyi, Mahmood Tazari, Markus Selzner, Nazia Selzner
BACKGROUND: The optimal vasodilator to avoid hepatic artery (HA) vasospasm during normothermic ex vivo liver perfusion (NEVLP) is yet to be determined. We compared safety and efficacy of BQ123 (endothelin1 antagonist), Epoprostenol (prostacyclin analogue), and Verapamil (calcium channel antagonist). METHODS: Livers from porcine heart beating donors were perfused for 3 hours and transplanted into recipient pigs. Four groups were compared: Group 1: livers perfused with a dose of 1...
November 20, 2017: Transplantation
https://www.readbyqxmd.com/read/29176869/successful-transplantation-of-porcine-liver-grafts-following-48-hour-normothermic-preservation
#14
Thomas Vogel, Jens G Brockmann, David Pigott, Desley A H Neil, Anand S Rathnasamy Muthusamy, Constantin C Coussios, Peter J Friend
Current cold storage organ preservation technique fails to preserve marginal donor grafts sufficiently. Evidence from large animal experiments suggests superiority of normothermic machine preservation of liver allografts. Long-term organ preservation using normothermic perfusion might not only allow organ viability assessment before transplantation, but also provide the means for further organ modifications under physiologic conditions. Previous research has shown that porcine livers can be transplanted successfully after normothermic preservation of 20 hours...
2017: PloS One
https://www.readbyqxmd.com/read/29159187/the-role-of-costimulation-blockade-in-solid-organ-and-islet-xenotransplantation
#15
REVIEW
Kannan P Samy, James R Butler, Ping Li, David K C Cooper, Burcin Ekser
Pig-to-human xenotransplantation offers a potential bridge to the growing disparity between patients with end-stage organ failure and graft availability. Early studies attempting to overcome cross-species barriers demonstrated robust humoral immune responses to discordant xenoantigens. Recent advances have led to highly efficient and targeted genomic editing, drastically altering the playing field towards rapid production of less immunogenic porcine tissues and even the discussion of human xenotransplantation trials...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29127105/epor-2-%C3%AE-cr-2-independendent-effects-of-low-dose-epoetin-%C3%AE-in-porcine-liver-transplantation
#16
Linus Kebschull, Leon Franz Christoph Theilmann, Annika Mohr, Wencke Uennigmann, Sandra Stoeppeler, Barbara Heitplatz, Hans-Ullrich Spiegel, Ralf Bahde, Daniel Michael Palmes, Felix Becker
Ischemia-reperfusion injury (IRI) remains a key component of graft damage during transplantation. Erythropoietin (EPO) induces anti-inflammatory and anti-apoptotic effects via the EPOR2 /βcR2 complex, with a potential risk of thrombosis. Previous work indicates that EPO has EPOR2 /βcR2 -independent protective effects via direct effects on the endothelium. As the EPOR2 /βcR2 receptor has a very low affinity for EPO, we aimed to test the hypothesis that EPO doses below the level that stimulate this receptor elicit cytoprotective effects via endothelial stimulation in a porcine liver transplantation model...
December 22, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29109530/a-clinical-scale-bioartificial-liver-developed-for-gmp-improved-clinical-parameters-of-liver-function-in-porcine-liver-failure
#17
Clare Selden, James Bundy, Eloy Erro, Eva Puschmann, Malcolm Miller, Delawir Kahn, Humphrey Hodgson, Barry Fuller, Jordi Gonzalez-Molina, Aurelie Le Lay, Stephanie Gibbons, Sherri Chalmers, Sunil Modi, Amy Thomas, Peter Kilbride, Agnes Isaacs, Richard Ginsburg, Helen Ilsley, David Thomson, Galya Chinnery, Ncedile Mankahla, Lizel Loo, C Wendy Spearman
Liver failure, whether arising directly from acute liver failure or from decompensated chronic liver disease is an increasing problem worldwide and results in many deaths. In the UK only 10% of individuals requiring a liver transplant receive one. Thus the need for alternative treatments is paramount. A BioArtificial Liver machine could temporarily replace the functions of the liver, buying time for the patient's liver to repair and regenerate. We have designed, implemented and tested a clinical-scale BioArtificial Liver machine containing a biomass derived from a hepatoblastoma cell-line cultured as three dimensional organoids, using a fluidised bed bioreactor, together with single-use bioprocessing equipment, with complete control of nutrient provision with feedback BioXpert recipe processes, and yielding good phenotypic liver functions...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29101678/liver-bioengineering-using-decellularized-whole-liver-scaffolds
#18
Iris Pla-Palacín, Pilar Sainz-Arnal, Sara Morini, Manuel Almeida, Pedro M Baptista
Currently, due to the progress made in the field of regenerative medicine, whole-organ bioengineering is becoming a valid alternative to cope with the shortages of organs for transplantation. In this chapter, we describe the main techniques carried out for pig liver bioengineering, which serves as an essential model for future human liver bioengineering. These include porcine whole-liver decellularization, endothelial and mesenchymal stem cell isolation, porcine ES-derived hepatoblasts, and scaffold recellularization using a bioreactor perfusion system...
November 4, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29057561/pre-clinical-results-in-pig-to-non-human-primate-islet-xenotransplantation-using-anti-cd40-antibody-2c10r4-based-immunosuppression
#19
Jun-Seop Shin, Jong-Min Kim, Byoung-Hoon Min, Il Hee Yoon, Hyun Je Kim, Jung-Sik Kim, Yong-Hee Kim, Seong-Jun Kang, Jiyeon Kim, Hee-Jung Kang, Dong-Gyun Lim, Eung-Soo Hwang, Jongwon Ha, Sang-Joon Kim, Wan Beom Park, Chung-Gyu Park
BACKGROUND: Islet transplantation is an effective therapy for selected patients with type 1 diabetes with labile glycemic control and hypoglycemic unawareness, but donor organs are limited. Islet xenotransplantation using porcine islets will potentially solve this problem. Although successful proof of concept studies using clinically inapplicable anti-CD154 monoclonal antibody (mAb) in pig-to-non-human primate (NHP) islet xenotransplantation has been demonstrated by several groups worldwide, potentially clinically applicable anti-CD40 (2C10R4) mAb-based studies have not been reported...
January 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29024427/combined-liver-kidney-perfusion-enhances-protective-effects-of-normothermic-perfusion-on-liver-grafts-from-donation-after-cardiac-death
#20
Xiaoshun He, Fei Ji, Zhiheng Zhang, Yunhua Tang, Lu Yang, Shanzhou Huang, Wenwen Li, Qiao Su, Wei Xiong, Zebin Zhu, Linhe Wang, Lei Lv, Jiyou Yao, Linan Zhang, Longjuan Zhang, Zhiyong Guo
It has been shown that combined liver-kidney normothermic machine perfusion (NMP) is able to better maintain the circuit's biochemical milieu. Nevertheless, whether the combined perfusion is superior to liver perfusion alone in protecting livers from donation after circulatory death (DCD) is unclear. We aimed to test the hypothesis and explored the mechanisms. Livers from 15 DCD pig donors were subjected to either static cold storage (group A), liver-alone NMP (group B), or combined liver-kidney NMP (group C)...
January 2018: Liver Transplantation
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