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https://www.readbyqxmd.com/read/28340694/composition-and-organization-of-the-pancreatic-extracellular-matrix-by-combined-methods-of-immunohistochemistry-proteomics-and-scanning-electron-microscopy
#1
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
#2
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
#3
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
#4
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...
February 13, 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
#5
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
#6
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 humandonor pancreata limits progress. Islet xenotransplantation, using pigs as sources of islet is a promising approach to overcome this limitation. The greatest obstacle is the primate immune/ inflammatory response to the pig islets, which may take the form of rapid early graft destruction (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...
February 3, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28130881/transplantation-of-hepatocytes-from-genetically-engineered-pigs-into-baboons
#7
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/28058735/safe-use-of-anti-cd154-monoclonal-antibody-in-pig-islet-xenotransplantation-in-monkeys
#8
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
#9
Nizar Mourad, Andrea Perota, Daela Xhema, Cesare Galli, Pierre Gianello
Porcine islets have notoriously low insulin secretion levels in response to glucose stimulation. While this is somehowexpected in the case of immature islets isolated from fetal and neonatal pigs, disappointingly low secretory responses are frequently reported in studies using <em>in vitro</em>-maturated fetal and neonatal islets and even fully-differentiated adult islets. Herein, we show that beta-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)...
November 22, 2016: 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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/27872471/recent-progress-in-xenotransplantation-with-emphasis-on-virological-safety
#14
Joachim Denner
Xenotransplantation is a new technology that may help to overcome the shortage of human tissues and organs available for the treatment of tissue and organ failure. Remarkable progress has recently been made in this field. First, understanding of the mechanisms of immunological rejection, mainly of the hyperacute rejection, allowed generating numerous genetically modified pigs to overcome rejection. Second, based on these genetically modified animals and new immunosuppression regimens, long-term survival of non-human primate recipients of heart, kidney, and islet cell cells has been reported...
November 22, 2016: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/27677465/no-perv-transmission-during-a-clinical-trial-of-pig-islet-cell-transplantation
#15
Vladimir A Morozov, Shaun Wynyard, Shinichi Matsumoto, Adrian Abalovich, Joachim Denner, Robert Elliott
Xenotransplantation of pig islet cells is a promising alternative for the treatment of diabetes with insulin and may help to prevent numerous late complications such as blindness and amputation. First encouraging results using porcine islets have been reported in preclinical animal models as well in the first clinical trial in New Zealand. The goal of this manuscript is to examine the biological safety of a second trial performed in Argentina, specifically in regards to the transmission of porcine endogenous retroviruses (PERVs) using improved detection methods As in the first trial encapsulated islet cells from the well-characterised Auckland Island pigs were used...
January 2, 2017: Virus Research
https://www.readbyqxmd.com/read/27586421/pancreatic-islets-methods-for-isolation-and-purification-of-juvenile-and-adult-pig-islets
#16
Heide Brandhorst, Paul R V Johnson, Daniel Brandhorst
The current situation of organ transplantation is mainly determined by the disbalance between the number of available organs and the number of patients on the waiting list. This obvious dilemma might be solved by the transplantation of porcine organs into human patients. The metabolic similarities which exist between both species made pancreatic islets of Langerhans to that donor tissue which will be most likely transplanted in human recipients. Nevertheless, the successful isolation of significant yields of viable porcine islets is extremely difficult and requires extensive experiences in the field...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27586419/the-different-faces-of-the-pancreatic-islet
#17
Midhat H Abdulreda, Rayner Rodriguez-Diaz, Over Cabrera, Alejandro Caicedo, Per-Olof Berggren
Type 1 diabetes (T1D) patients who receive pancreatic islet transplant experience significant improvement in their quality-of-life. This comes primarily through improved control of blood sugar levels, restored awareness of hypoglycemia, and prevention of serious and potentially life-threatening diabetes-associated complications, such as kidney failure, heart and vascular disease, stroke, nerve damage, and blindness. Therefore, beta cell replacement through transplantation of isolated islets is an important option in the treatment of T1D...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27569971/human-endothelial-protein-c-receptor-overexpression-protects-intraportal-islet-grafts-in-mice
#18
H Gock, K F E Lee, L Murray-Segal, T B Mysore, A J F d'Apice, E J Salvaris, P J Cowan
Islet transplantation can potentially cure type 1 diabetes mellitus, but it is limited by a shortage of human donors as well as by islet graft destruction by inflammatory and thrombotic mechanisms. A possible solution to these problems is to use genetically modified pig islets. Endothelial protein C receptor (EPCR) enhances protein C activation and regulates coagulation, inflammation, and apoptosis. We hypothesized that human EPCR (hEPCR) expression on donor islets would improve graft survival and function...
July 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27517501/genetic-strategies-to-bring-islet-xenotransplantation-to-the-clinic
#19
Wayne J Hawthorne, Andrew M Lew, Helen E Thomas
PURPOSE OF REVIEW: Despite the benefits of islet and pancreas allotransplantation, their widespread use in type 1 diabetes is limited because of the paucity of suitable donors. Porcine xenotransplantation offers an alternative, and advances in genetic modification of pigs have opened up new potential for its clinical use. This review outlines the barriers to successful islet xenotransplantation, and genetic modifications that have been tested to overcome these. RECENT FINDINGS: Islets from pigs lacking α1,3-galactosyltransferase, to prevent hyperacute rejection, are now used as a background strain for further genetic modifications...
October 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27511303/molecular-immunology-profiles-of-monkeys-following-xenografting-with-the-islets-and-heart-of-%C3%AE-1-3-galactosyltransferase-knockout-pigs
#20
Sun A Ock, Jungkyu Lee, Keon Bong Oh, Seongsoo Hwang, Ik Jin Yun, Curie Ahn, Hyun Keun Chee, Hwajung Kim, Jae Berm Park, Sung Joo Kim, Youngim Kim, Gi-Sun Im, EungWoo Park
Effective immunosuppression strategies and genetically modified animals have been used to prevent hyperacute and acute xenograft rejection; however, the underlying mechanisms remain unknown. In this study, we evaluated the expression of a comprehensive set of immune system-related genes (89 genes, including five housekeeping genes) in the blood of cynomolgus monkeys (~5 yr old) used as graft recipients, before and after the xenografting of the islets and heart from single and double α-1,3-galactosyltransferase (GalT) knockout (KO) pigs (<6 weeks old)...
September 2016: Xenotransplantation
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