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Pig liver transplant

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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
#1
Nicolas Goldaracena, Vinzent N Spetzler, Juan Echeverri, Johan M Kaths, Vera Cherepanov, Robert Persson, Michael G Hodges, Harry LA Janssen, Nazia Selzner, David R Grant, Jordan J Feld, Markus 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-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). Miravirsen absorption, miR-122 sequestration and miR-122 target gene derepression were determined before and after LT...
November 2, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27663858/can-transcutaneous-near-infrared-spectroscopy-detect-severe-hepatic-ischemia-a-juvenile-porcine-model
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/27556578/anti-inflammatory-signaling-during-ex-vivo-liver-perfusion-improves-the-preservation-of-pig-liver-grafts-before-transplantation
#5
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
INTRODUCTION: Normothermic ex vivo liver perfusion (NEVLP) improves graft preservation by avoiding cold ischemic injury. We investigated whether the protective effects of NEVLP can be further improved by applying strategies targeted on reducing the activation of pro-inflammatory cytokines during perfusion. METHODS: Livers retrieved under heart beating conditions were perfused for 4 hours. Following preservation period, pig liver transplantation was performed. In group-1 (n=5) anti-inflammatory strategies (alprostadil, n-acetylcysteine, CO and sevoflurane, subnormothermic temperature (33°C)) were applied...
August 24, 2016: Liver Transplantation
https://www.readbyqxmd.com/read/27510266/efficient-liver-repopulation-of-transplanted-hepatocyte-prevents-cirrhosis-in-a-rat-model-of-hereditary-tyrosinemia-type-i
#6
Ludi Zhang, Yanjiao Shao, Lu Li, Feng Tian, Jin Cen, Xiaotao Chen, Dan Hu, Yan Zhou, Weifen Xie, Yunwen Zheng, Yuan Ji, Mingyao Liu, Dali Li, Lijian Hui
Hereditary tyrosinemia type I (HT1) is caused by a deficiency in the enzyme fumarylacetoacetate hydrolase (Fah). Fah-deficient mice and pigs are phenotypically analogous to human HT1, but do not recapitulate all the chronic features of the human disorder, especially liver fibrosis and cirrhosis. Rats as an important model organism for biomedical research have many advantages over other animal models. Genome engineering in rats is limited till the availability of new gene editing technologies. Using the recently developed CRISPR/Cas9 technique, we generated Fah(-/-) rats...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27496504/concentration-of-tumor-necrosis-factor-%C3%AE-and-interleukin-1%C3%AE-in-isolated-porcine-liver-depending-on-type-of-transgenesis
#7
P Roman, G Budziński, A Suszka-Świtek, A Caban, G Oczkowicz, R Wiaderkiewicz, F Ryszka, Z Smorąg, L Cierpka
BACKGROUND: Transgenic animals may serve as organ donors in human organ transplantation. However, the number of the studies addressing all doubts related to this issue is currently insufficient for the clinical application of this approach. The aim of this study was to analyze the hepatic tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) synthesis during a 24-hour cold preservation of the transgenic pig liver, depending on the type of transgenesis. MATERIALS AND METHODS: The study was carried out on wild-type and transgenic pig livers with transferred human α1,2-fucosyltransferase (FUT) and/or α-galactosidase (GAL) gene (four groups; n = 6)...
June 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27496501/caspase-3-expression-and-alt-ast-and-ggt-activity-after-24-hours-of-porcine-liver-cold-storage-depending-on-the-type-of-transgenesis
#8
P Roman, G Budziński, A Suszka-Świtek, A Caban, G Oczkowicz, E Czech, F Ryszka, R Wiaderkiewicz, Z Smorąg, L Cierpka
BACKGROUND: Because of an insufficient number of human organs for transplantation, xenotransplantation may become an effective alternative. We aimed to analyze if the type of transgenesis has an influence on the hepatic caspase-3 expression, the enzyme that executes apoptosis as well as ALT, AST, and GGT activity after 24 hours of cold storage. METHODS: The experiment was carried out on the 24 livers of Polish White Landrace pigs carrying human α1,2-fucosyltransferase and/or α-galactosidase (GAL) genes and livers without this genetic modification (control)...
June 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27464750/curative-ex-vivo-liver-directed-gene-therapy-in-a-pig-model-of-hereditary-tyrosinemia-type-1
#9
Raymond D Hickey, Shennen A Mao, Jaime Glorioso, Faysal Elgilani, Bruce Amiot, Harvey Chen, Piero Rinaldo, Ronald Marler, Huailei Jiang, Timothy R DeGrado, Lukkana Suksanpaisan, Michael K O'Connor, Brittany L Freeman, Samar H Ibrahim, Kah Whye Peng, Cary O Harding, Chak-Sum Ho, Markus Grompe, Yasuhiro Ikeda, Joseph B Lillegard, Stephen J Russell, Scott L Nyberg
We tested the hypothesis that ex vivo hepatocyte gene therapy can correct the metabolic disorder in fumarylacetoacetate hydrolase-deficient (Fah(-/-)) pigs, a large animal model of hereditary tyrosinemia type 1 (HT1). Recipient Fah(-/-) pigs underwent partial liver resection and hepatocyte isolation by collagenase digestion. Hepatocytes were transduced with one or both of the lentiviral vectors expressing the therapeutic Fah and the reporter sodium-iodide symporter (Nis) genes under control of the thyroxine-binding globulin promoter...
July 27, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27464486/porcine-antigen-specific-ifn-%C3%AE-elispot-as-a-potentially-valuable-tool-for-monitoring-cellular-immune-responses-in-pig-to-non-human-primate-islet-xenotransplantation
#10
Hyun-Je Kim, Il-Hee Yoon, Byoung-Hoon Min, Yong-Hee Kim, Jun-Seop Shin, Jong-Min Kim, Jung-Sik Kim, Hye-Young Nam, Won-Woo Lee, Chung-Gyu Park
BACKGROUND: Recent progress in xenotransplantation of porcine islets to non-human primates (NHPs) gives hope for human clinical trials in the near future. Thus, implementation of an appropriate monitoring method to detect the development of detrimental porcine antigen-specific cellular immune responses is necessary. The enzyme-linked immunospot (ELISpot) assay has been widely used to monitor antigen-specific alloreactive T-cell responses in humans; however, the utility of porcine islet-specific ELISpot assay has not yet been thoroughly evaluated for pig-to-NHPs intraportal islet xenotransplantation...
July 2016: Xenotransplantation
https://www.readbyqxmd.com/read/27428714/pig-liver-xenotransplantation-a-review-of-progress-toward-the-clinic
#11
David K C Cooper, Ke-Feng Dou, Kai-Shan Tao, Zhao-Xu Yang, A Joseph Tector, Burcin Ekser
Experience with clinical liver xenotransplantation has largely involved the transplantation of livers from nonhuman primates. Experience with pig livers has been scarce. This brief review will be restricted to assessing the potential therapeutic impact of pig liver xenotransplantation in acute liver failure and the remaining barriers that currently do not justify clinical trials. A relatively new surgical technique of heterotopic pig liver xenotransplantation is described that might play a role in bridging a patient with acute liver failure until either the native liver recovers or a suitable liver allograft is obtained...
October 2016: Transplantation
https://www.readbyqxmd.com/read/27320595/subnormothermic-machine-perfusion-preservation-with-rewarming-for-donation-after-cardiac-death-liver-grafts-in-pigs
#12
M Furukori, N Matsuno, L T Meng, T Shonaka, Y Nishikawa, K Imai, H Obara, H Furukawa
BACKGROUND: The use of grafts from donors after cardiac death (DCD) would greatly contribute to the expansion of the donor organ pool. However, the implementation of such a strategy requires the development of novel preservation methods to recover from changes owing to warm ischemia. The aim of this study was to evaluate the effectiveness of subnormothermic machine perfusion (MP) preservation with rewarming for porcine DCD liver grafts for transplantation. METHODS: Porcine livers were perfused with newly developed MP system...
May 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27251849/cannulation-selection-of-portal-venous-and-splenic-venous-catheterization-in-venovenous-bypass-of-swine-orthotopic-liver-transplantation
#13
Meng-Yuan Wang, Meng-Hao Wang, Yong Peng, Hai-Bo You, Xian-Feng Chen, Lei Zhao, Lin Gan, Min Li, Jin-Zheng Li, Jian-Ping Gong, Xu-Hong Li
BACKGROUND The aim of this study was to compare the hemodynamic changes in 2 different cannulations in portal system (portal venous catheterization and splenic venous catheterization) during venovenous bypass (VVB) of swine orthotopic liver transplantation (OLT) MATERIAL AND METHODS Thirty pairs (a total of 60) of healthy Duroc pigs were selected for OLT. According to the difference of cannulation in portal venous system during VVB, these pigs were divided into 2 groups: the PVC group (pigs with portal venous catheterization, n=15) and the SVC group (pigs with splenic venous catheterization, n=15)...
2016: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/27194381/efficacy-of-fluidized-bed-bioartificial-liver-in-treating-fulminant-hepatic-failure-in-pigs-a-metabolomics-study
#14
Pengcheng Zhou, Li Shao, Lifu Zhao, Guoliang Lv, Xiaoping Pan, Anye Zhang, Jianzhou Li, Ning Zhou, Deying Chen, Lanjuan Li
Bioartificial livers may act as a promising therapy for fulminant hepatic failure (FHF) with better accessibility and less injury compared to orthotopic liver transplantation. This study aims to evaluate the efficacy and safety of a fluidized bed bioartificial liver (FBBAL) and to explore its therapeutic mechanisms based on metabolomics. FHF was induced by D-galactosamine. Eighteen hours later, pigs were treated with an FBBAL containing encapsulated primary porcine hepatocytes (B group), with a sham FBBAL (containing cell-free capsules, S group) or with only intensive care (C group) for 6 h...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27138018/radiopaque-biodegradable-stent-for-duct-to-duct-biliary-reconstruction-in-pigs
#15
Yoshisato Tanimoto, Hirotaka Tashiro, Yoshihiro Mikuriya, Shintaro Kuroda, Masakazu Hashimoto, Tsuyoshi Kobayashi, Tokunori Taniura, Hideki Ohdan
BACKGROUND: Biliary stricture is a common cause of morbidity after liver transplantation. We previously developed a duct-to-duct biliary anastomosis technique using a biodegradable stent tube and confirmed the feasibility and safety of biliary stent use. However, the duration and mechanism of biliary stent absorption in the common bile duct remain unclear. MATERIALS AND METHODS: Radiopaque biodegradable biliary stents were created using a copolymer of L-lactide and ε-caprolactone (70: 30) and coated with barium sulfate...
June 2016: Langenbeck's Archives of Surgery
https://www.readbyqxmd.com/read/27134015/heparin-gelatin-mixture-improves-vascular-reconstruction-efficiency-and-hepatic-function-in-bioengineered-livers
#16
Kamal Hany Hussein, Kyung-Mee Park, Kyung-Sun Kang, Heung-Myong Woo
UNLABELLED: Whole organ decellularization is a cell removal process that creates a natural extracellular matrix for use in transplantation. A lack of an intact endothelial layer in the vascular network of decellularized organs results in blood clotting even with anti-coagulation treatment. Furthermore, shear stress caused by blood flow may affect reseeded parenchymal cells. We hypothesized that a heparin-gelatin mixture (HG) can act as an antithrombotic coating reagent and induce attachment and migration of endothelial cells (ECs) on vascular wall surfaces within decellularized livers, with subsequent parenchymal cell function enhancement...
July 1, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27041638/modulation-of-liver-tolerance-by-conventional-and-nonconventional-antigen-presenting-cells-and-regulatory-immune-cells
#17
REVIEW
Andrea Kristina Horst, Katrin Neumann, Linda Diehl, Gisa Tiegs
The liver is a tolerogenic organ with exquisite mechanisms of immune regulation that ensure upkeep of local and systemic immune tolerance to self and foreign antigens, but that is also able to mount effective immune responses against pathogens. The immune privilege of liver allografts was recognized first in pigs in spite of major histo-compatibility complex mismatch, and termed the "liver tolerance effect". Furthermore, liver transplants are spontaneously accepted with only low-dose immunosuppression, and induce tolerance for non-hepatic co-transplanted allografts of the same donor...
May 2016: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/27037634/protective-role-of-normothermic-machine-perfusion-during-reduced-size-liver-transplantation-in-pigs
#18
Zhi-Bin Zhang, Wei Gao, Yuan Shi, Lei Liu, Ning Ma, Jing Chen, Zhi-Jun Zhu
The purpose of this study is to explore whether normothermic machine perfusion (NMP) preservation is superior to cold preservation during reduced-size liver transplantation (RSLT) in pigs. Twenty-four healthy Ba-Ma mini pigs were used (aged >13 months; weight 25-35 kg; regardless of sex). The animals were randomized into 2 groups. In group A (NMP), donor livers were harvested without warm ischemia time and heartbeats and then were connected to the NMP system to reduce the livers' size under the normothermic condition...
July 2016: Liver Transplantation
https://www.readbyqxmd.com/read/26999803/succinate-accumulation-and-ischemia-reperfusion-injury-of-mice-but-not-men-a-study-in-renal-ischemia-reperfusion
#19
L G M Wijermars, A F Schaapherder, S Kostidis, R C I Wüst, J H Lindeman
A recent seminal paper implicated ischemia-related succinate accumulation followed by succinate-driven reactive oxygen species formation as a key driver of ischemia-reperfusion injury. Although the data show that the mechanism is universal for all organs tested (kidney, liver, heart, and brain), a remaining question is to what extent these observations in mice translate to humans. We showed in this study that succinate accumulation is not a universal event during ischemia and does not occur during renal graft procurement; in fact, tissue succinate content progressively decreased with increasing graft ischemia time (p < 0...
September 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/26884426/quantitative-evaluation-of-human-bone-mesenchymal-stem-cells-rescuing-fulminant-hepatic-failure-in-pigs
#20
Dongyan Shi, Jianing Zhang, Qian Zhou, Jiaojiao Xin, Jing Jiang, Longyan Jiang, Tianzhou Wu, Jiang Li, Wenchao Ding, Jun Li, Suwan Sun, Jianzhou Li, Ning Zhou, Liyuan Zhang, Linfeng Jin, Shaorui Hao, Pengcheng Chen, Hongcui Cao, Mingding Li, Lanjuan Li, Xin Chen, Jun Li
OBJECTIVE: Stem cell transplantation provides a promising alternative for the treatment of fulminant hepatic failure (FHF). However, it lacks fundamental understanding of stem cells' activities. Our objective was to clarify stem cell-recipient interactions for overcoming barriers to clinical application. DESIGN: We used an in-house large-animal (pig) model of FHF rescue by human bone marrow mesenchymal stem cells (hBMSCs) and profiled the cells' activities. The control and transplantation groups of pigs (n=15 per group) both received a D-galactosamine (D-Gal) injection (1...
February 16, 2016: Gut
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