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Pig liver transplant

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https://www.readbyqxmd.com/read/29127105/epor2-%C3%A3-cr2-independendent-effects-of-low-dose-epoetin-a-in-porcine-liver-transplantation
#1
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 the key component of graft damage during transplantation. Erythropoietin (EPO) induces anti-inflammatory and anti-apoptotic effects via the EPOR2/ßcR2-complex, with the potential risk of thrombosis. Previous work indicates that EPO has EPOR2/ßcR2-independent protective effects via direct effects on the endothelium. As the EPOR2/ßcR2-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...
November 10, 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
#2
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
#3
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
#4
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...
October 22, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29024427/combined-liver-kidney-perfusion-enhances-protective-effects-of-normothermic-perfusion-on-livers-grafts-from-donation-after-cardiac-death
#5
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 showed 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 cardiac 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 (Group A), liver alone NMP group (Group B), or combined liver-kidney NMP group (Group C)...
October 10, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28944602/hepatitis-e-virus-and-related-viruses-in-wild-domestic-and-zoo-animals-a-review
#6
REVIEW
C Spahr, T Knauf-Witzens, T Vahlenkamp, R G Ulrich, R Johne
Hepatitis E is a human disease mainly characterized by acute liver illness, which is caused by infection with the hepatitis E virus (HEV). Large hepatitis E outbreaks have been described in developing countries; however, the disease is also increasingly recognized in industrialized countries. Mortality rates up to 25% have been described for pregnant women during outbreaks in developing countries. In addition, chronic disease courses could be observed in immunocompromised transplant patients. Whereas the HEV genotypes 1 and 2 are mainly confined to humans, genotypes 3 and 4 are also found in animals and can be zoonotically transmitted to humans...
September 24, 2017: Zoonoses and Public Health
https://www.readbyqxmd.com/read/28854432/ursolic-acid-improves-liver-transplantation-and-inhibits-apoptosis-in-miniature-pigs-using-donation-after-cardiac-death
#7
Wei Zhou, Li Lin, Ying Cheng, Yongfeng Liu
BACKGROUND: Ursolic acid (UA) possesses extensive pharmacological activities, including anti-oxidation, anti-infection, anti-inflammation, anti-tumor, liver protection. This study was designed to investigate the effect of UA on liver transplantation after liver transplantation using donation after cardiac death (DCD), and to assess the mechanisms. METHODS: 24 healthy experimental pigs were randomly divided into control and experimental groups. Each group received six DCD liver transplantations...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28730558/transplantation-sites-for-porcine-islets
#8
Rebecca A Stokes, Denbigh M Simond, Heather Burns, Anita T Patel, Philip J O'Connell, Jenny E Gunton, Wayne J Hawthorne
AIMS/HYPOTHESIS: Xenotransplantation has great potential to provide beta cell replacement and thereby provide a cure for large numbers of people with type 1 diabetes. Crucial to the success of xenotransplantation is establishment of the most viable sites for transplantation. METHODS: We compared porcine islet tissue transplanted into kidney, liver and spleen in pig recipients as assessed by blood glucose levels and IVGTT. RESULTS: Kidney was the superior site for porcine islet tissue transplantation, followed by liver then spleen...
October 2017: Diabetologia
https://www.readbyqxmd.com/read/28724761/isg15-modulates-type-i-interferon-signaling-and-the-antiviral-response-during-hepatitis-e-virus-replication
#9
Harini Sooryanarain, Adam J Rogers, Dianjun Cao, Mary Etna R Haac, Yogesh A Karpe, Xiang-Jin Meng
Hepatitis E virus (HEV), a single-stranded positive-sense RNA virus, generally causes self-limiting acute viral hepatitis, although chronic HEV infection has recently become a significant clinical problem in immunocompromised individuals, especially in solid-organ transplant recipients. Innate immunity, via the type I interferon (IFN) response, plays an important role during the initial stages of a viral infection. IFN-stimulated gene 15 (ISG15), an IFN-induced ubiquitin-like protein, is known to have an immunomodulatory role and can have a direct antiviral effect on a wide spectrum of virus families...
October 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28714241/cytokine-profiles-in-tibetan-macaques-following-%C3%AE-1-3-galactosyltransferase-knockout-pig-liver-xenotransplantation
#10
Zhuochao Zhang, Xiao Li, Hong Zhang, Xuan Zhang, Hui Chen, Dengke Pan, Hongchen Ji, Liang Zhou, Juan Ling, Jingshi Zhou, Shuqiang Yue, Desheng Wang, Zhaoxu Yang, Kaishan Tao, Kefeng Dou
BACKGROUND: Pig-to-nonhuman primate orthotopic liver xenotransplantation is often accompanied by thrombocytopenia and coagulation disorders. Furthermore, the release of cytokines can trigger cascade reactions of coagulation and immune attacks within transplant recipients. To better elucidate the process of inflammation in liver xenograft recipients, we utilized a modified heterotopic auxiliary liver xenotransplantation model for xeno-immunological research. We studied the cytokine profiles and the relationship between cytokine levels and xenograft function after liver xenotransplantation...
July 17, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28704336/plasmatic-villin-1-is-a-novel-in-vivo-marker-of-proximal-tubular-cell-injury-during-renal-ischemia-reperfusion
#11
Jean-Paul Decuypere, Laurens J Ceulemans, Tine Wylin, Wim Martinet, Diethard Monbaliu, Jacques Pirenne, Ina Jochmans
BACKGROUND: Early detection of acute kidney injury (AKI), a common condition with a high mortality risk, can be facilitated by specific and reliable biomarkers. Villin 1, a protein typically found in the brush borders of proximal tubular cells, has been detected in urine of patients with AKI, but its possible release in plasma remains unexplored. METHODS: We measured the presence of villin 1 by immunohistochemistry on kidney sections and by Western blotting in plasma samples from rats subjected to renal ischemia-reperfusion injury, pigs subjected to renal transplantation and liver transplantation patients that developed AKI...
November 2017: Transplantation
https://www.readbyqxmd.com/read/28630420/functional-evaluation-of-a-bioartificial-liver-support-system-using-immobilized-hepatocyte-spheroids-in-a-porcine-model-of-acute-liver-failure
#12
Ji-Hyun Lee, Doo-Hoon Lee, Sanghoon Lee, Choon Hyuck David Kwon, Jae-Nam Ryu, Jeong-Kwon Noh, In Keun Jang, Hey-Jung Park, Hee-Hoon Yoon, Jung-Keug Park, Young-Jin Kim, Sung-Koo Kim, Suk-Koo Lee
Bioartificial livers (BAL) may offer acute liver failure (ALF) patients an opportunity for cure without liver transplantation. We evaluated the efficacy of a spheroid-based BAL system, containing aggregates of porcine hepatocytes, in a porcine model of ALF. ALF pigs were divided into three groups. The control group consisted of treatment naïve pigs (n = 5), blank group consisted of pigs that were attached to the BAL system not containing hepatocytes for 12 hours (n = 5) and BAL group consisted of pigs that were attached to the BAL containing hepatocytes for 12 hours (n = 5)...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630341/pig-model-mimicking-chronic-hepatitis-e-virus-infection-in-immunocompromised-patients-to-assess-immune-correlates-during-chronicity
#13
Dianjun Cao, Qian M Cao, Sakthivel Subramaniam, Danielle M Yugo, C Lynn Heffron, Adam J Rogers, Scott P Kenney, Debin Tian, Shannon R Matzinger, Christopher Overend, Nicholas Catanzaro, Tanya LeRoith, Heng Wang, Pablo Piñeyro, Nicole Lindstrom, Sherrie Clark-Deener, Lijuan Yuan, Xiang-Jin Meng
Chronic hepatitis E virus (HEV) infection is a significant clinical problem in immunocompromised individuals such as organ transplant recipients, although the mechanism remains unknown because of the lack of an animal model. We successfully developed a pig model of chronic HEV infection and examined immune correlates leading to chronicity. The conditions of immunocompromised patients were mimicked by treating pigs with an immunosuppressive regimen including cyclosporine, azathioprine, and prednisolone. Immunocompromised pigs infected with HEV progressed to chronicity, because 8/10 drug-treated HEV-infected pigs continued fecal virus shedding beyond the acute phase of infection, whereas the majority (7/10) of mock-treated HEV-infected pigs cleared fecal viral shedding at 8 wk postinfection...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28489305/prolonged-survival-following-pig-to-primate-liver-xenotransplantation-utilizing-exogenous-coagulation-factors-and-costimulation-blockade
#14
J A Shah, M S Patel, N Elias, N Navarro-Alvarez, I Rosales, R A Wilkinson, N J Louras, M Hertl, J A Fishman, R B Colvin, A B Cosimi, J F Markmann, D H Sachs, P A Vagefi
Since the first attempt of pig-to-primate liver xenotransplantation (LXT) in 1968, survival has been limited. We evaluated a model utilizing α-1,3-galactosyltransferase knockout donors, continuous posttransplant infusion of human prothrombin concentrate complex, and immunosuppression including anti-thymocyte globulin, FK-506, methylprednisone, and costimulation blockade (belatacept, n = 3 or anti-CD40 mAb, n = 1) to extend survival. Baboon 1 remained well until postoperative day (POD) 25, when euthanasia was required because of cholestasis and plantar ulcers...
August 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28444910/characterization-of-porcine-endogenous-retrovirus-expression-in-neonatal-and-adult-pig-pancreatic-islets
#15
Nizar I Mourad, Claire Crossan, Victoria Cruikshank, Linda Scobie, Pierre Gianello
BACKGROUND: Pig islets represent an alternative to the current modes of treatment for patients with diabetes. However, the concerns over pathogen transmission including that of PERV limit their immediate, widespread usage in humans. It has been previously demonstrated that PERV copy number and particularly expression levels can vary considerably between individuals and within different tissues of a single animal. In general, expression levels have been found to be particularly low in the pancreas compared to other porcine tissues suggesting a reduced risk associated with the use of this tissue...
July 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28436075/does-a-meso-caval-shunt-have-positive-effects-in-a-pig-large-for-size-liver-transplantation-model
#16
Ana Cristina Aoun Tannuri, Daniel de Albuquerque Rangel Moreira, Alessandro Belon, Maria Cecília Mendonça Coelho, Josiane Oliveira Gonçalves, Suellen Serafini, Uenis Tannuri
In pediatric liver transplantations with LFS grafts, higher incidences of graft dysfunction probably occur due to IRI. It was postulated that increasing the blood supply to the graft by means of a meso-caval shunt could ameliorate the IRI. Eleven pigs underwent liver transplantation and were divided into two groups: LFS and LFS+SHUNT group. A series of flowmetric, metabolic, histologic, and molecular studies were performed. No significant metabolic differences were observed between the groups. One hour after reperfusion, portal flow was significantly lower in the recipients than in the donors, proving that the graft was maintained in low portal blood flow, although the shunt could promote a transient increase in the portal blood flow and a decrease in the arterial flow...
August 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28417501/d-dimer-level-in-association-with-humoral-responses-negatively-correlates-with-survival-of-porcine-islet-grafts-in-non-human-primates-with-immunosuppression
#17
Hee Jung Kang, Haneulnari Lee, Eun Mi Park, Jong-Min Kim, Byoung-Hoon Min, Chung-Gyu Park
BACKGROUND: Several immunosuppression (IS) regimens achieve long-term graft survival in non-human primates (NHPs) after porcine islet transplantation (PITx), but their success rates vary. To understand the mechanism of graft loss, we investigated the relationships between graft survival and humoral or inflammatory responses for maintenance IS in NHPs after PITx. METHODS: Islets purified from adult wild-type pigs were intraportally transplanted into streptozotocin-induced diabetic rhesus monkeys...
April 18, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28403128/an-oxygenated-and-transportable-machine-perfusion-system-fully-rescues-liver-grafts-exposed-to-lethal-ischemic-damage-in-a-pig-model-of-dcd-liver-transplantation
#18
Philippe Compagnon, Eric Levesque, Hassen Hentati, Mara Disabato, Julien Calderaro, Cyrille Feray, Anne Corlu, José Laurent Cohen, Ismail Ben Mosbah, Daniel Azoulay
BACKGROUND: Control of warm ischemia (WI) lesions that occur with donation after circulatory death (DCD) would significantly increase the donor pool for liver transplantation. We aimed to determine whether a novel, oxygenated and hypothermic machine perfusion device (HMP Airdrive system) improves the quality of livers derived from DCDs using a large animal model. METHODS: Cardiac arrest was induced in female large white pigs by intravenous injection of potassium chloride...
July 2017: Transplantation
https://www.readbyqxmd.com/read/28388830/the-release-of-microrna-122-during-liver-preservation-is-associated-with-early-allograft-dysfunction-and-graft-survival-after-transplantation
#19
Jasmijn W Selten, Cornelia J Verhoeven, Veerle Heedfeld, Henk P Roest, Jeroen de Jonge, Jacques Pirenne, Jos van Pelt, Jan N M Ijzermans, Diethard Monbaliu, Luc J W van der Laan
Early allograft dysfunction (EAD) after liver transplantation (LT) is associated with inferior graft survival. EAD is more prevalent in grafts from donation after circulatory death (DCD). However, accurate prediction of liver function remains difficult because of the lack of specific biomarkers. Recent experimental and clinical studies highlight the potential of hepatocyte-derived microRNAs (miRNAs) as sensitive, stable, and specific biomarkers of liver injury. The aim of this study was to determine whether miRNAs in graft preservation fluid are predictive for EAD after clinical LT and in an experimental DCD model...
July 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28372287/organ-reconstruction-dream-or-reality-for%C3%A2-the%C3%A2-future
#20
REVIEW
J-F Stoltz, L Zhang, J S Ye, N De Isla
The relevance of research on reconstructed organs is justified by the lack of organs available for transplant and the growing needs for the ageing population. The development of a reconstructed organ involves two parallel complementary steps: de-cellularization of the organ with the need to maintain the structural integrity of the extracellular matrix and vascular network and re-cellularization of the scaffold with stem cells or resident cells.Whole organ engineering for liver, heart, lung or kidneys, is particularly difficult because of the structural complexity of organs and heterogeneity of cells...
2017: Bio-medical Materials and Engineering
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