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Xenotransplantation

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https://www.readbyqxmd.com/read/28303661/immunological-and-physiological-observations-in-baboons-with-life-supporting-genetically-engineered-pig-kidney-grafts
#1
Hayato Iwase, Hidetaka Hara, Mohamed Ezzelarab, Tao Li, Zhongqiang Zhang, Bingsi Gao, Hong Liu, Cassandra Long, Yi Wang, Amy Cassano, Edwin Klein, Carol Phelps, David Ayares, Abhinav Humar, Martin Wijkstrom, David K C Cooper
BACKGROUND: Genetically engineered pigs could provide a source of kidneys for clinical transplantation. The two longest kidney graft survivals reported to date have been 136 and 310 days, but graft survival >30 days has been unusual until recently. METHODS: Donor pigs (n=4) were on an α1,3-galactosyltransferase gene-knockout (GTKO)/human complement regulatory protein (CD46) background (GTKO/CD46). In addition, the pigs were transgenic for at least one human coagulation regulatory protein...
March 17, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28303603/human-il-6-il-17-il-1%C3%AE-and-tnf-%C3%AE-differently-regulate-the-expression-of-pro-inflammatory-related-genes-tissue-factor-and-swine-leukocyte-antigen-class-i-in-porcine-aortic-endothelial-cells
#2
Hanchao Gao, Lu Liu, Yanli Zhao, Hidetaka Hara, Pengfei Chen, Jia Xu, Jia Tang, Ling Wei, Zesong Li, David K C Cooper, Zhiming Cai, Lisha Mou
BACKGROUND: Pro-inflammatory cytokines play important pathological effects in various diseases and allotransplantation; however, their pathological role in xenotransplantation remains elusive. In pig-to-human cell or organ transplantation, whether porcine cells or organs are activated by human cytokines or not as an important question needs to be investigated. METHODS: We investigated the effect of human IL-6, IFN-γ, IL-17, IL-1β, and TNF-α in xenotransplantation using several in vitro models and porcine aortic endothelial cells (PAECs) as target cells...
March 17, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28294424/therapeutic-regulation-of-systemic-inflammation-in-xenograft-recipients
#3
Hayato Iwase, Hong Liu, Tao Li, Zhongquiang Zhang, Bingsi Gao, Hidetaka Hara, Martin Wijkstrom, Cassandra Long, Ryan Saari, David Ayares, David K C Cooper, Mohamed B Ezzelarab
Inflammation is known to preclude tolerance after transplantation. We have previously shown that systemic inflammation in xenograft recipients (SIXR) precedes activation of coagulation in the absence of T cell responses. Accordingly, SIXR may amplify innate and adaptive immune responses against xenografts after pig-to-primate xenotransplantation, even with efficient immunosuppressive therapy. We evaluated the impact of anti-inflammatory agents on pro-inflammatory cytokines and chemokines in pig artery patch and heart xenograft recipients...
March 12, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28261903/testing-of-microencapsulated-porcine-hepatocytes-in-a-new-model-of-fulminant-liver-failure-in-baboons
#4
Zurab Machaidze, Heidi Yeh, Lingling Wei, Christian Schuetz, Michele Carvello, Antonino Sgroi, Rex N Smith, Henk-Jan Schuurman, David H Sachs, Philippe Morel, James F Markmann, Léo H Bühler
BACKGROUND: There is no standard therapy for acute liver failure. Hepatocyte transplantation has been proposed for temporary liver function support, while the injured liver regenerates or while waiting for transplantation. We have previously shown such efficacy for microencapsulated porcine hepatocytes in mice with fulminant liver failure. We aimed to establish a large animal model for fulminant liver failure to assess the efficacy of microencapsulated porcine hepatocytes in temporary liver function support...
March 5, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28261878/hemodynamic-and-perioperative-management-in-two-different-preclinical-pig-to-baboon-cardiac-xenotransplantation-models
#5
Tanja Mayr, Andreas Bauer, Bruno Reichart, Sonja Guethoff, Uwe Schoenmann, Matthias Längin, Alessandro Panelli, Alexander Kind, Paolo Brenner, Jan-Michael Abicht
BACKGROUND: The perioperative phase of preclinical cardiac xenotransplantations significantly affects the experimental outcome. Moderate or even severe hemodynamic and respiratory impairment occurs frequently in baboons after receiving a cardiac transplant. The perioperative management of such postoperative instability is very demanding, especially in the experimental setting. We compared perioperative changes of hemodynamic and laboratory findings during orthotopic and heterotopic thoracic cardiac xenotransplantations and describe our monitoring, treatment and intensive care...
March 5, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28258595/transgenic-expression-of-human-leukocyte-antigen-e-attenuates-galko-hcd46-porcine-lung-xenograft-injury
#6
Christopher T Laird, Lars Burdorf, Beth M French, Natalia Kubicki, Xiangfei Cheng, Gheorghe Braileanu, Wenji Sun, Natalie A O'Neill, Arielle Cimeno, Dawn Parsell, Edward So, Andrea Bähr, Nikolai Klymiuk, Carol J Phelps, David Ayares, Agnes M Azimzadeh, Richard N Pierson
BACKGROUND: Lung xenografts remain susceptible to loss of vascular barrier function within hours in spite of significant incremental advances based on genetic engineering to remove the Gal 1,3-αGal antigen (GalTKO) and express human membrane cofactor protein (hCD46). Natural killer cells rapidly disappear from the blood during perfusion of GalTKO.hCD46 porcine lungs with human blood and presumably are sequestered within the lung vasculature. Here we asked whether porcine expression of the human NK cell inhibitory ligand HLA-E and β2 microglobulin inhibits GalTKO...
March 3, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28258588/gastrostomy-tube-placement-for-long-term-oral-drug-administration-in-non-human-primates
#7
Jong-Min Kim, Jun-Seop Shin, Byoung-Hoon Min, Jung-Sik Kim, Il-Hee Yoon, Won-Young Jeong, Ga-Eul Lee, Min-Sun Kim, Ju-Eun Kim, Chung-Gyu Park
BACKGROUND: Non-human primates (NHPs) are often used as recipients in preclinical transplantation research that in most cases involves administration of various drugs including immunosuppressants. Long-term oral drug administration, particularly tacrolimus, is challenging in the transplant recipient NHPs. Oral drug administration method using the mixture of drug and fruit juice has been used in NHPs, but this is not always effective in all monkeys. To those monkeys who are poorly compliant, oral drug administration in restraint or administration using gastrostomy tube should be necessary...
March 3, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28160329/xenotransplantation-literature-update-november-december-2016
#8
Magie Steinhoff, Raza Naqvi, Christopher Burlak
No abstract text is available yet for this article.
February 4, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28130881/transplantation-of-hepatocytes-from-genetically-engineered-pigs-into-baboons
#9
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...
January 28, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28130838/production-of-high-quality-islets-from-goettingen-minipigs-choice-of-organ-preservation-solution-donor-pool-and-optimal-cold-ischemia-time
#10
Anja Steffen, Thomas Kiss, Janine Schmid, Undine Schubert, Sophie Heinke, Susann Lehmann, Stefan Bornstein, Barbara Ludwig, Stefan Ludwig
BACKGROUND: The transplantation of porcine islets into man might soon become reality for patients with type 1 diabetes mellitus. Therefore, porcine islets of high quality and quantity, and a scalable isolation process with strict quality control will be an unconditional prerequisite to enable the best possible transplantation graft. In this study, we provide a comparative study evaluating islet isolation outcome and in vitro survival based upon donor age, organ preservation solution (OPS), and cold ischemia time (CIT)...
January 28, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28130792/klotho-attenuated-antibody-mediated-porcine-endothelial-cell-activation-and-injury
#11
Lu Liu, Hanchao Gao, Chungu Hong, Chen He, Dengke Pan, Yifan Dai, Hidetaka Hara, David K C Cooper, Zesong Li, Zhiming Cai, Lisha Mou
Long-term success in pig-to-primate xenotransplantation is currently hampered by acute vascular rejection (AVR), characterized by endothelial cell (EC) activation and injury. Klotho has anti-apoptotic, anti-inflammatory effects on EC and protects EC against reactive oxygen species, rendering klotho a promising molecule to control AVR. In this study, porcine ECs were pre-incubated with klotho and then exposed to xenoreactive antibodies and complement. Real-time PCR revealed that klotho suppressed antibody-induced pro-inflammatory gene expression of VCAM-1 and IL-1α...
January 28, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28127796/construction-of-bioengineered-hepatic-tissue-derived-from-human-umbilical-cord-mesenchymal-stem-cells-via-aggregation-culture-in-porcine-decellularized-liver-scaffolds
#12
Yi Li, Qiong Wu, Yujia Wang, Li Li, Fei Chen, Yujun Shi, Ji Bao, Hong Bu
BACKGROUND: An individualized, tissue-engineered liver suitable for transplanting into a patient with liver disease would be of great benefit to the patient and the healthcare system. The tissue-engineered liver would possess the functions of the original healthy organ. Two fields of study, (i) using decellularized tissue as cell scaffolding, and (ii) stem cell differentiation into functional cells, are coming together to make this concept feasible. The decellularized liver scaffolds (DLS) can interact with cells to promote cell differentiation and signal transduction and three-dimensional (3D) stem cell aggregations can maintain the phenotypes and improve functions of stem cells after differentiation by undergoing cell-cell contact...
January 26, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28102609/immunogenicity-of-hepatic-differentiated-human-umbilical-cord-mesenchymal-stem-cells-promoted-by-porcine-decellularized-liver-scaffolds
#13
Yi Li, Qiong Wu, Yujia Wang, Li Li, Fei Chen, Yujun Shi, Hong Bu, Ji Bao
Cell-based approaches, including hepatocyte transplantation and tissue-engineered livers, offer promising alternatives and are expected to help support patients with liver diseases until liver transplantation or recovery via regeneration of the damaged liver. However, the success of cell therapies remains dependent on how well the cells are accepted after transplantation and is directly related to their degree of immunogenicity. In this study, hepatic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) was induced in the traditional monolayer (2D) culture and newly established three-dimensional (3D) aggregation culture with the porcine decellularized liver scaffold (DLS) system (3D-DLS)...
January 19, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28101961/antibody-formation-towards-porcine-tissue-in-patients-implanted-with-crosslinked-heart-valves-is-directed-to-antigenic-tissue-proteins-and-%C3%AE-gal-epitopes-and-is-reduced-in-healthy-vegetarian-subjects
#14
Ulrike Böer, Falk F R Buettner, Ariane Schridde, Melanie Klingenberg, Samir Sarikouch, Axel Haverich, Mathias Wilhelmi
BACKGROUND: Glutaraldehyde-fixed porcine heart valves (ga-pV) are one of the most frequently used substitutes for insufficient aortic and pulmonary heart valves which, however, degenerate after 10-15 years. Yet, xeno-immunogenicity of ga-pV in humans including identification of immunogens still needs to be investigated. We here determined the immunogenicity of ga-pV in patients with respect to antibody formation, identity of immunogens and potential options to reduce antibody levels. METHODS: Levels of tissue-specific and anti-αGal antibodies were determined retrospectively in patients who received ga-pV for 51 months (n=4), 25 months (n=6) or 5 months (n=4) and compared to age-matched untreated subjects (n=10) or younger subjects with or without vegetarian diet (n=12/15)...
January 18, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28054735/initial-study-of-%C3%AE-1-3-galactosyltransferase-gene-knockout-cd46-pig-full-thickness-corneal-xenografts-in-rhesus-monkeys
#15
Xiaojuan Dong, Hidetaka Hara, Ying Wang, Li Wang, Yingnan Zhang, David K C Cooper, Yifan Dai, Zhiqiang Pan
BACKGROUND: To investigate graft survival after full-thickness corneal xenotransplantation from α1,3-galactosyltransferase gene-knockout (GTKO) pigs expressing a human complement regulatory protein (GTKO/CD46 pigs) in rhesus monkeys. METHODS: Rhesus monkeys (n=10) were transplanted with full-thickness corneas from wild-type (WT; n=4) and GTKO/CD46 (n=4) pigs or from monkeys (n=2). All recipient monkeys received post-transplant subconjunctival injections of betamethasone...
January 5, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28247507/development-of-retrocorneal-membrane-following-pig-to-monkey-penetrating-keratoplasty
#16
Whayoung Lee, Alex Mammen, Deepinder K Dhaliwal, Cassandra Long, Yuko Miyagawa, David Ayares, David K C Cooper, Hidetaka Hara
Recent reports of long-term survival after wild-type (WT) pig-to-monkey corneal xenotransplantation are encouraging. We experienced the rapid development of retrocorneal membranes, a rare complication after corneal allotransplantation (although seen in infants and young children). The original specific aim of the study was to determine the factors associated with successful (young) pig corneal transplantation in monkeys. However, when it was obvious that retrocorneal membranes rapidly developed, our aims became to determine the factors involved in its development after both WT and Genetically engineered (GE ) pig corneal xenotransplantation and to investigate the characteristics of the retrocorneal membrane...
January 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28247506/the-effect-of-hypoxia-on-free-and-encapsulated-adult-porcine-islets-an-in-vitro-study
#17
Sudhakar Muthyala, Susan Safley, Kereen Gordan, Graham Barber, Collin Weber, Athanassios Sambanis
BACKGROUND: Adult porcine islets (APIs) constitute a promising alternative to human islets in treating type 1 diabetes. The intrahepatic site has been used in preclinical primate studies of API xenografts; however, an estimated two-thirds of donor islets are destroyed after intraportal infusion due to a number of factors, including the instant blood-mediated inflammatory reaction (IBMIR), immunosuppressant toxicity, and poor reestablishment of extracellular matrix connections. Intraperitoneal (ip) transplantation of non-vascularized encapsulated islets offers several advantages over intrahepatic transplantation of free islets, including avoidance of IBMIR, immunoprotection, accommodation of a larger graft volume, and reduced risk of hemorrhage...
January 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28058735/safe-use-of-anti-cd154-monoclonal-antibody-in-pig-islet-xenotransplantation-in-monkeys
#18
Rita Bottino, Michael F Knoll, Joshua Graeme-Wilson, Edwin C Klein, David Ayares, Massimo Trucco, David K C Cooper
Anti-CD154mAb is a powerful co-stimulation blockade agent that is efficacious in preventing rejection, even in xenogeneic settings. It has been used in the majority of successful long-term pig-to-non-human primate islet transplantation models. However, its clinical use was halted as a result of thromboembolic complications that were also observed in preclinical and clinical organ transplantation models. An anti-CD154mAb was administered to 14 streptozotocin-induced diabetic cynomolgus monkey recipients of porcine islets, some of which received the agent for many months...
January 2017: Xenotransplantation
https://www.readbyqxmd.com/read/27677785/complement-c3-inhibitor-cp40-attenuates-xenoreactions-in-pig%C3%A2-hearts-perfused-with-human-blood
#19
Jan-Michael Abicht, Ioannis Kourtzelis, Bruno Reichart, Sophia Koutsogiannaki, Alexandra Primikyri, John D Lambris, Triantafyllos Chavakis, Lesca Holdt, Alexander Kind, Sonja Guethoff, Tanja Mayr
BACKGROUND: The complement system plays a crucial role in acute xenogeneic reactions after cardiac transplantation. We used an ex vivo perfusion model to investigate the effect of Cp40, a compstatin analog and potent inhibitor of complement at the level of C3. METHODS: Fifteen wild-type pig hearts were explanted, cardiopleged, and reperfused ex vivo after 150 minutes of cold ischemia. Hearts were challenged in a biventricular working heart mode to evaluate cardiac perfusion and function...
January 2017: Xenotransplantation
https://www.readbyqxmd.com/read/27897334/xenotransplantation-literature-update-september-october-2016
#20
AnAn Hua, Magie Steinhoff, Christopher Burlak
No abstract text is available yet for this article.
November 2016: Xenotransplantation
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