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Pig liver transplant

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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
#1
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
#2
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...
June 19, 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
#3
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...
May 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28444910/characterization-of-porcine-endogenous-retrovirus-expression-in-neonatal-and-adult-pig-pancreatic-islets
#4
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...
April 26, 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
#5
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...
April 24, 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
#6
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
#7
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 IV injection of potassium chloride...
April 11, 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
#8
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
#9
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
https://www.readbyqxmd.com/read/28334710/prevention-of-tlr9-pathway-in-warm-ischemia-in-porcine-donor-liver-after-cardiac-death
#10
Zigong Shao, Baoping Jiao, Dehui Yi, Tingting Liu, Qi Pan, Ying Cheng, Hao Liu
OBJECTIVE: To investigate effect of warm ischemia after cardiac death on activation of TLR9 pathway in porcine liver. METHODS: Donor of cardiac death (DCD) model was established with Duroc, Landrace, Large White crossbred pigs. Liver tissues from the animals were harvested at 0, 5, 10, 15, 25 and 30 minutes after warm ischemia for analysis of expression of TLR9, IRF7, IFN-β, and TNF-α at mRNA and protein levels by real-time PCR and western blot, respectively, and for assessment of NF-κB/DNA binding activity by western blot detection of p65 protein...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28328941/cynomolgus-monkeys-are-successfully-and-persistently-infected-with-hepatitis-e-virus-genotype-3-hev-3-after-long-term-immunosuppressive-therapy
#11
Noemi Rovaris Gardinali, Juliana Rodrigues Guimarães, Juliana Gil Melgaço, Yohan Britto Kevorkian, Fernanda de Oliveira Bottino, Yasmine Rangel Vieira, Aline Campos de Azevedo da Silva, Douglas Pereira Pinto, Laís Bastos da Fonseca, Leandro Schiavo Vilhena, Edilson Uiechi, Maria Cristina Carlan da Silva, Julio Moran, Renato Sérgio Marchevsky, Oswaldo Gonçalves Cruz, Rodrigo Alejandro Arellano Otonel, Amauri Alcindo Alfieri, Jaqueline Mendes de Oliveira, Ana Maria Coimbra Gaspar, Marcelo Alves Pinto
Epidemiological studies found that hepatitis E virus genotype 3 (HEV-3) infection was associated with chronic hepatitis and cirrhosis in immunocompromised patients. Our study aimed to investigate the relationship between the host immunosuppressive status and the occurrence of HEV-related chronic hepatitis. Here we describe a successful experimental study, using cynomolgus monkeys previously treated with tacrolimus, a potent calcineurin inhibitor immunosuppressant, and infected with a Brazilian HEV-3 strain isolated from naturally infected pigs...
2017: PloS One
https://www.readbyqxmd.com/read/28295889/acute-hepatitis-e-virus-infection-causing-acute-liver-failure-requiring-living-donor-liver-transplantation-in-a-non-pregnant-immunocompetent-woman
#12
Iris Wai Sum Li, Kenneth Siu Ho Chok
We report a rare case of acute liver failure from acute hepatitis E virus (HEV) in a non-pregnant woman without comorbidities who survived after liver transplantation. The source was likely consumption of partially cooked pig liver. HEV genotype 3 is the second most common genotype causing acute hepatitis E in developed countries. Fulminant hepatitis E rarely occurs without a risk factor, as in our patient. Vigilant monitoring for chronic hepatitis E in post-transplant immunocompromised patients is needed.
March 14, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28130881/transplantation-of-hepatocytes-from-genetically-engineered-pigs-into-baboons
#13
Hayato Iwase, Hong Liu, Eva Schmelzer, Mohamed Ezzelarab, Martin Wijkstrom, Hidetaka Hara, Whayoung Lee, Jagjit Singh, Cassandra Long, Eric Lagasse, Jörg C Gerlach, David K C Cooper, Bruno Gridelli
BACKGROUND: Some patients with acute or acute-on-chronic hepatic failure die before a suitable human liver allograft becomes available. Encouraging results have been achieved in such patients by the transplantation of human hepatocyte progenitor cells from fetal liver tissue. The aim of the study was to explore survival of hepatocytes from genetically engineered pigs after direct injection into the spleen and other selected sites in immunosuppressed baboons to monitor the immune response and the metabolic function and survival of the transplanted hepatocytes...
March 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28053091/fumarylacetoacetate-hydrolase-knock-out-rabbit-model-for-hereditary-tyrosinemia-type-1
#14
Li Li, Quanjun Zhang, Huaqiang Yang, Qingjian Zou, Chengdan Lai, Fei Jiang, Ping Zhao, Zhiwei Luo, Jiayin Yang, Qian Chen, Yan Wang, Philip N Newsome, Jon Frampton, Patrick H Maxwell, Wenjuan Li, Shuhan Chen, Dongye Wang, Tak-Shing Siu, Sidney Tam, Hung-Fat Tse, Baoming Qin, Xichen Bao, Miguel A Esteban, Liangxue Lai
Hereditary tyrosinemia type 1 (HT1) is a severe human autosomal recessive disorder caused by the deficiency of fumarylacetoacetate hydroxylase (FAH), an enzyme catalyzing the last step in the tyrosine degradation pathway. Lack of FAH causes accumulation of toxic metabolites (fumarylacetoacetate and succinylacetone) in blood and tissues, ultimately resulting in severe liver and kidney damage with onset that ranges from infancy to adolescence. This tissue damage is lethal but can be controlled by administration of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), which inhibits tyrosine catabolism upstream of the generation of fumarylacetoacetate and succinylacetone...
March 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28039700/extended-hepatectomy-using-the-bipolar-tissue-sealer-an-experimental-model-of-small-for-size-syndrome-in-pigs
#15
Antonios Athanasiou, Michael Kontos, Emmanouil Pikoulis, John Griniatsos, Apostolos Papalois, Eleftherios Spartalis, Demetrios Moris, Evangelos Felekouras, Theodoros Liakakos
PURPOSE: After liver transplantation with a small-for-size liver graft or after extensive hepatectomy for liver malignancies or other non malignant conditions with an insufficient liver volume, the survival of patients depends on liver regeneration. This study was carried out in order to create a new porcine model for the study of small-for-size syndrome (SFSS) after extensive hepatectomy. METHODS: In the present study we used 23 domestic Landrace pigs weighing 28...
November 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/27993199/the-beneficial-role-of-simultaneous-splenectomy-after-extended-hepatectomy-experimental-study-in-pigs
#16
Antonios Athanasiou, Apostolos Papalois, Michael Kontos, John Griniatsos, Dimitrios Liakopoulos, Eleftherios Spartalis, George Agrogiannis, Theodoros Liakakos, Emmanouil Pikoulis
BACKGROUND: The role of hepatic hemodynamic modulation in the development of "small-for-size" syndrome (SFSS) after extended hepatectomy (EH) or living-donor liver transplantation is still controversial. We have designed an experimental study to investigate the effect of hemodynamic parameters of the liver circulation on the development of SFSS after EH in a porcine model. METHODS: Eighteen pigs were randomly divided into two groups: group A has received EH (75%-80%) without splenectomy, and group B with EH and simultaneous splenectomy was carried out...
February 2017: Journal of Surgical Research
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
#17
N Goldaracena, V N Spetzler, J Echeverri, J M Kaths, V Cherepanov, R Persson, M R 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)...
April 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/27663858/can-transcutaneous-near-infrared-spectroscopy-detect-severe-hepatic-ischemia-a-juvenile-porcine-model
#18
Justin J Skowno, Jonathan S Karpelowsky, Nicola R Watts, David G Little
BACKGROUND: Vascular complications following pediatric liver transplantation occur in 8-10% of cases, and no continuous, non-invasive monitoring for this problem exists. Near infrared spectroscopy (NIRS) allows non-invasive, continuous, transcutaneous assessment of hemoglobin oxygenation (StO2 ) 1-4 cm below the skin surface. AIMS: We hypothesized that transcutaneous NIRS would be able to detect severe hepatic ischemia, and tested this in an animal model using 15-20 kg and 5-7 kg juvenile pigs...
December 2016: Paediatric Anaesthesia
https://www.readbyqxmd.com/read/27610014/hepatitis-e-discovery-global-impact-control-and-cure
#19
REVIEW
Mohammad S Khuroo, Mehnaaz S Khuroo, Naira S Khuroo
Hepatitis E was identified as an epidemic of non-A, non-B hepatitis from Kashmir, India in 1978. Hepatitis E virus (HEV), the etiological agent is the sole member of family Hepeviridae. The virus has marked heterogeneity and infects many animals like bats, camel, chicken, deer, boar, mongoose, pigs, rats, rabbit and cutthroat trout. Hepatitis E is a disease with a major global impact and has two distinct epidemiological patterns. Hepatitis E is an imperative health issue in developing nations, transmitted through sullied water and happens most every now in young adults...
August 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27596934/comparison-of-methods-for-isolating-primary-hepatocytes-from-mini-pigs
#20
Yi Li, Yujia Wang, Qiong Wu, Li Li, Yujun Shi, Hong Bu, Ji Bao
Successful porcine hepatocyte isolation is crucial for the development of bioartificial liver devices and hepatocyte transplantation. Serva collagenase NB grades are formulated collagenases that are suitable for various tissue isolation applications. N-acetylcysteine (NAC) can improve the viability of human hepatocytes. The aim of this study was to compare the effectiveness of two collagenases and effect of NAC on hepatocyte isolation from porcine liver tissue. Porcine hepatocytes were isolated using the perfusion method from Bama mini pigs assigned to the Serva NB 4 group (n=6), the Serva NB 8 group (n=6), or the NB 8+NAC group (n=6)...
September 2016: Xenotransplantation
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