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https://www.readbyqxmd.com/read/28632821/encapsulated-islet-transplantation-where-do-we-stand
#1
Vijayaganapathy Vaithilingam, Sumeet Bal, Bernard E Tuch
Transplantation of pancreatic islets encapsulated within immuno-protective microcapsules is a strategy that has the potential to overcome graft rejection without the need for toxic immunosuppressive medication. However, despite promising preclinical studies, clinical trials using encapsulated islets have lacked long-term efficacy, and although generally considered clinically safe, have not been encouraging overall. One of the major factors limiting the long-term function of encapsulated islets is the host's immunological reaction to the transplanted graft which is often manifested as pericapsular fibrotic overgrowth (PFO)...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28620237/lea29y-expression-in-transgenic-neonatal-porcine-islet-like-cluster-promotes-long-lasting-xenograft-survival-in-humanized-mice-without-immunosuppressive-therapy
#2
L Wolf-van Buerck, M Schuster, F S Oduncu, A Baehr, T Mayr, S Guethoff, J Abicht, B Reichart, N Klymiuk, E Wolf, J Seissler
Genetically engineered pigs are a promising source for islet cell transplantation in type 1 diabetes, but the strong human anti-pig immune response prevents its successful clinical application. Here we studied the efficacy of neonatal porcine islet-like cell clusters (NPICCs) overexpressing LEA29Y, a high-affinity variant of the T cell co-stimulation inhibitor CTLA-4Ig, to engraft and restore normoglycemia after transplantation into streptozotocin-diabetic NOD-SCID IL2rγ(-/-) (NSG) mice stably reconstituted with a human immune system...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28616498/xenotransplantation-a-special-case-of-one-health
#3
REVIEW
Joachim Denner
The chronic shortage of human transplants to treat tissue and organ failure has led to the development of xenotransplantation, the transplantation of cells, tissues and organs from another species to human recipients. For a number of reasons, pigs are best suited as donor animals. Successful, routine xenotransplantation would have an enormous impact on the health of the human population, including the young, who sometimes require a replacement organ or islet cells, but especially the elderly, who more often suffer the consequences of organ failure...
June 2017: One Health
https://www.readbyqxmd.com/read/28472471/successful-immunosuppressant-free-heterotopic-transplantation-of-tracheal-allografts-in-the-pig
#4
Julien De Wolf, Mathias Brieu, Christophe Zawadzki, Alexandre Ung, Eric Kipnis, Ramadan Jashari, Thomas Hubert, Pierre Fayoux, Christophe Mariette, Marie-Christine Copin, Alain Wurtz
OBJECTIVES: It has been demonstrated that both heterotopic and orthotopic transplants of epithelium-denuded cryopreserved tracheal allografts are feasible in immunosuppressant-free rabbits. Validation of these results in large animals is required before considering clinical applications. We evaluated the viability, immune tolerance and strain properties of such tracheal allografts heterotopically transplanted in a pig model. METHODS: Ten tracheal segments, 5 short (5 rings) and 5 long (10 rings), were obtained from male Landrace pigs...
May 2, 2017: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/28444910/characterization-of-porcine-endogenous-retrovirus-expression-in-neonatal-and-adult-pig-pancreatic-islets
#5
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/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/28397351/the-resurgence-of-xenotransplantation
#7
Peter J Cowan, A Joseph Tector
There has been an upsurge of interest in xenotransplantation in recent years. This resurgence can attributed to a combination of factors. First, there has been a dramatic improvement in efficacy in several preclinical models, with maximum xenograft survival times increasing to 950 days for islets, 945 days for hearts, and 310 days for kidneys. Second, the rapid development of genome editing technology (particularly the advent of CRISPR/Cas9) has revolutionized the capacity to generate new donor pigs with multiple protective genetic modifications; what once took many years to achieve can now be performed in months, with much greater precision and scope...
April 11, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28340694/composition-and-organization-of-the-pancreatic-extracellular-matrix-by-combined-methods-of-immunohistochemistry-proteomics-and-scanning-electron-microscopy
#8
S Vigier, H Gagnon, K Bourgade, K Klarskov, T Fülöp, P Vermette
The epidemic expansion of diabetes is a major concern of public health. A promising treatment is the transplantation of islets of Langerhans isolated from the whole pancreas but the yields of islets isolation and the rates of successful engraftments still have to be improved to make this therapy effective. The extracellular matrix (ECM) of the pancreatic tissue is partially lost during the isolation process and a comprehensive knowledge of the pancreatic ECM composition and organization could identify targets to improve islets isolation and transplantation or highlight new therapeutics for pancreatic diseases...
January 2017: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/28322428/xenotransplantation-where-do-we-stand-in-2016
#9
Gisella L Puga Yung, Robert Rieben, Leo Bühler, Henk-Jan Schuurman, Jörg Seebach
Worldwide, there is a constant rise in the number of patients with end-stage organ failure in critical need for transplants, but the number of organs/cells available from deceased or living human donors is limited. Xenotransplantation using pig organs/tissues repre-sents a potential solution for this shortage; however, it has been hampered by a number of mainly immuno-logical hurdles. Remarkable progress was presented at the latest biennial (13th) international congress of the International Xenotransplantation Association, November 2015 in Melbourne, Australia, and the American Transplant Congress, May 2016 in Boston, USA...
March 21, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28271465/porcine-islet-xenografts-a-clinical-source-of-%C3%A3-cell-grafts
#10
REVIEW
Bassem F Salama, Gregory S Korbutt
PURPOSE OF REVIEW: Diabetes is medical and social burden affecting millions around the world. Despite intensive therapy, insulin fails to maintain adequate glucose homeostasis and often results in episodes of hypoglycemic unawareness. Islet transplantation is a propitious replacement therapy, and incremental improvements in islet isolation and immunosuppressive drugs have made this procedure a feasible option. Shortage of donors, graft loss, and toxic immunosuppressive agents are few of many hurdles against making human allogenic islet transplantation a routine procedure...
March 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28254450/diabetic-phenotype-of-transgenic-pigs-introduced-by-dominant-negative-mutant-hepatocyte-nuclear-factor-1%C3%AE
#11
Kazuhiro Umeyama, Masami Nakajima, Takashi Yokoo, Masaki Nagaya, Hiroshi Nagashima
AIM: The present study aimed to identify the characteristics of genetically modified pigs carrying a mutant human gene as a research model for diabetes and its complications. METHODS: We developed a transgenic cloned pig (founder, male) carrying a mutant gene, i.e., human HNF-1α (P291fsinsC), which is responsible for maturity-onset diabetes of the young type 3. Transgenic progeny obtained via the artificial insemination of wild type (WT) sows with the cryopreserved sperm derived from the founder pig was pathologically examined...
May 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28190419/seaweed-extracts-and-galacto-oligosaccharides-improve-intestinal-health-in-pigs-following-salmonella-typhimurium-challenge
#12
M A Bouwhuis, M J McDonnell, T Sweeney, A Mukhopadhya, C J O'Shea, J V O'Doherty
Pork and pork products are recognised as vehicles of Salmonella Typhimurium infection in humans. Seaweed-derived polysaccharides (SWE) and galacto-oligosaccharides (GOS) have shown to exhibit antimicrobial, prebiotic and immunomodulatory activity. The objective of this study was to assess the effects of dietary GOS and SWE supplementation on reducing S. Typhimurium numbers and intestinal inflammation in vivo. In total, 30 pigs (n=10/treatment, BW 30.9 kg) were randomly assigned to three dietary treatments: (1) basal diet; (2) basal diet+2...
February 13, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/28155815/pig-to-primate-islet-xenotransplantation-past-present-and-future
#13
Zhengzhao Liu, Wenbao Hu, Tian He, Yifan Dai, Hidetaka Hara, Rita Bottino, David K C Cooper, Zhiming Cai, Lisha Mou
Islet allotransplantation results in increasing success in treating type 1 diabetes, but the shortage of deceased human donor pancreata limits progress. Islet xenotransplantation, using pigs as a source of islets, is a promising approach to overcome this limitation. The greatest obstacle is the primate immune/inflammatory response to the porcine (pig) islets, which may take the form of rapid early graft rejection (the instant blood-mediated inflammatory reaction) or T-cell-mediated rejection. These problems are being resolved by the genetic engineering of the source pigs combined with improved immunosuppressive therapy...
June 9, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28130881/transplantation-of-hepatocytes-from-genetically-engineered-pigs-into-baboons
#14
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/28058735/safe-use-of-anti-cd154-monoclonal-antibody-in-pig-islet-xenotransplantation-in-monkeys
#15
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/27938490/transgenic-expression-of-glucagon-like-peptide-1-glp-1-and-activated-muscarinic-receptor-m3r-significantly-improves-pig-islet-secretory-function
#16
Nizar I Mourad, Andrea Perota, Daela Xhema, Cesare Galli, Pierre Gianello
Porcine islets show notoriously low insulin secretion levels in response to glucose stimulation. While this is somehow expected in the case of immature islets isolated from fetal and neonatal pigs, disappointingly low secretory responses are frequently reported in studies using in vitro-maturated fetal and neonatal islets and even fully differentiated adult islets. Herein we show that β-cell-specific expression of a modified glucagon-like peptide-1 (GLP-1) and of a constitutively activated type 3 muscarinic receptor (M3R) efficiently amplifies glucose-stimulated insulin secretion (GSIS)...
May 9, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/27938471/human-recombinant-antithrombin-atryn-%C3%A2-administration-improves-survival-and-prevents-intravascular-coagulation-after-intraportal-islet-transplantation-in-a-piglet-model
#17
Valery Gmyr, Caroline Bonner, Ericka Moerman, Antoine Tournoys, Nathalie Delalleau, Audrey Quenon, Julien Thevenet, Mikael Chetboun, Julie Kerr-Conte, François Pattou, Thomas Hubert, Merce Jourdain
Human islet transplantation is a viable treatment option for type 1 diabetes mellitus (T1DM). However, pancreatic islet inflammation after transplantation induced by innate immune responses is likely to hinder graft function. This is mediated by incompatibility between islets and the blood interface, known as instant blood-mediated inflammatory reaction (IBMIR). Herein we hypothesized that portal venous administration of islet cells with human recombinant antithrombin (ATryn®), a serine protease inhibitor (serpin), which plays a central role in the physiological regulation of coagulation and exerts indirect anti-inflammatory activities, may offset coagulation abnormalities such as disseminated intravascular coagulation (DIC) and IBMIR...
February 16, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/27931512/xenotransplanted-pig-sertoli-cells-inhibit-both-the-alternative-and-classical-pathways-of-complement-mediated-cell-lysis-while-pig-islets-are-killed
#18
Kandis Wright, Rachel Dziuk, Payal Mital, Gurvinder Kaur, Jannette M Dufour
Xenotransplantation has vast clinical potential but is limited by the potent immune responses generated against xenogeneic tissue. Immune-privileged Sertoli cells (SCs) survive xenotransplantation long term (90 days) without immunosuppression, making SCs an ideal model to identify xenograft survival mechanisms. Xenograft rejection includes the binding of natural and induced antibodies and the activation of the complement cascade. Using an in vitro cytotoxicity assay, wherein cells were cultured with human serum and complement, we demonstrated that neonatal pig SCs (NPSCs) are resistant to complement-mediated cell lysis and express complement inhibitory factors, membrane cofactor protein (MCP; CD46), and decay-accelerating factor (DAF; CD55) at significantly higher levels than neonatal pig islets (NPIs), which served as non-immune-privileged controls...
November 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27909715/a-new-scaffold-containing-small-intestinal-submucosa-and-mesenchymal-stem-cells-improves-pancreatic-islet-function-and-survival-in%C3%A2-vitro-and-in%C3%A2-vivo
#19
Dan Wang, Xiaoming Ding, Wujun Xue, Jin Zheng, Xiaohui Tian, Yang Li, Xiaohong Wang, Huanjin Song, Hua Liu, Xiaohui Luo
It is unknown whether a scaffold containing both small intestinal submucosa (SIS) and mesenchymal stem cells (MSCs) for transplantation may improve pancreatic islet function and survival. In this study, we examined the effects of a SIS-MSC scaffold on islet function and survival in vitro and in vivo. MSCs and pancreatic islets were isolated from Sprague-Dawley rats, and SIS was isolated from Bamei pigs. The islets were apportioned among 3 experimental groups as follows: SIS-islets, SIS-MSC-islets and control-islets...
January 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27893617/differential-role-of-b-cells-and-il-17-versus-ifn-%C3%AE-during-early-and-late-rejection-of-pig-islet-xenografts-in-mice
#20
Hee Kap Kang, Shusen Wang, Anil Dangi, Xiaomin Zhang, Amar Singh, Lei Zhang, James M Rosati, Wilma Suarez-Pinzon, Xuelian Deng, Xiaoyan Chen, Edward B Thorp, Bernhard J Hering, Stephen D Miller, Xunrong Luo
BACKGROUND: Xenogeneic islet transplantation is an emerging therapeutic option for diabetic patients. However, immunological tolerance to xenogeneic islets remains a challenge. METHODS: The current study used a pig-to-mouse discordant xenogeneic islet transplant model to examine anti-donor xenogeneic immune responses during early and late rejection, and to determine experimental therapeutic interventions that promote durable pig islet xenograft survival. RESULTS: We found that during early acute rejection of pig islet xenografts, the rejecting hosts exhibited a heavy graft infiltration with B220 B cells and a robust anti-pig antibody production...
November 23, 2016: Transplantation
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