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https://www.readbyqxmd.com/read/27872471/recent-progress-in-xenotransplantation-with-emphasis-on-virological-safety
#1
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/27862363/a-comprehensive-microbiological-safety-approach-for-agarose-encapsulated-porcine-islets-intended-for-clinical-trials
#2
Lawrence S Gazda, James Collins, Archie Lovatt, Robert W Holdcraft, Merribeth J Morin, Daniel Galbraith, Melanie Graham, Melissa A Laramore, Christine Maclean, John Black, Euan W Milne, Douglas G Marthaler, Horatiu V Vinerean, Michelle M Michalak, Deborah Hoffer, Steven Richter, Richard D Hall, Barry H Smith
BACKGROUND: The use of porcine islets to replace insulin-producing islet β-cells, destroyed during the diabetogenic disease process, presents distinct challenges if this option is to become a therapeutic reality for the treatment of type 1 diabetes. These challenges include a thorough evaluation of the microbiological safety of the islets. In this study, we describe a robust porcine islet-screening program that provides a high level of confidence in the microbiological safety of porcine islets suitable for clinical trials...
November 11, 2016: Xenotransplantation
https://www.readbyqxmd.com/read/27843954/continuous-quadrupole-magnetic-separation-of-islets-during-digestion-improves-purified-porcine-islet-viability
#3
Bradley P Weegman, Venkata Sunil Kumar Sajja, Thomas M Suszynski, Michael D Rizzari, William E Scott Iii, Jennifer P Kitzmann, Kate R Mueller, Thomas R Hanley, David J Kennedy, Paul W Todd, Appakalai N Balamurugan, Bernhard J Hering, Klearchos K Papas
Islet transplantation (ITx) is an emerging and promising therapy for patients with uncontrolled type 1 diabetes. The islet isolation and purification processes require exposure to extended cold ischemia, warm-enzymatic digestion, mechanical agitation, and use of damaging chemicals for density gradient separation (DG), all of which reduce viable islet yield. In this paper, we describe initial proof-of-concept studies exploring quadrupole magnetic separation (QMS) of islets as an alternative to DG to reduce exposure to these harsh conditions...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27830180/optimizing-porcine-islet-isolation-to-markedly-reduce-enzyme-consumption-without-sacrificing-islet-yield-or-function
#4
Robert W Holdcraft, Michael L Green, Andrew G Breite, Lisa Circle, Eric D Meyer, Hollie Adkins, Steven G Harbeck, Barry H Smith, Lawrence S Gazda
BACKGROUND: Human allogeneic islet transplantation for treatment of type 1 diabetes provides numerous clinical benefits, such as fewer episodes of hypoglycemic unawareness and tighter control of blood glucose levels. Availability of human pancreas for clinical and research use, however, is severely limited. Porcine pancreas offers an abundant source of tissue for optimization of islet isolation methodology and future clinical transplantation, thereby increasing patient access to this potentially lifesaving procedure...
July 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27773813/effect-of-cross-sensitization-between-xeno-and-allo-antigens-on-subsequent-allogeneic-and-xenogeneic-pancreatic-islet-transplantation-in-a-murine-model
#5
Hyun-Je Kim, Nari Byun, Ohsang Kwon, Chung-Gyu Park
The number of patients in need of organ transplantation is continuously on the rise. However, because of organ donor shortage, xenotransplantation has been highlighted as an alternative. Among the various porcine organs and tissues, porcine islets are considered to be the best-matching implantable candidates for clinical application based on recent progress in nonhuman primate pre-clinical studies. Nevertheless, before initiation of clinical trials, it should be confirmed whether the requisite xeno-antigen sensitization would have a deleterious effect on subsequent allo-transplantation or vice versa...
October 20, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27738948/methods-for-microencapsulated-porcine-islet-production
#6
Masayuki Shimoda, Shinichi Matsumoto
Allogeneic islet transplantation has become a viable option for the treatment of unstable type 1 diabetes; however, donor shortage and the necessity for immunosuppressive drugs are two major drawbacks of this treatment. Microencapsulated porcine islets can solve both of these drawbacks, and clinical trials have been conducted. Previous clinical trials demonstrated the safety and marginal efficacy of this treatment; therefore, it is necessary to improve its efficacy. The production of microencapsulated porcine islets consists of pancreas procurement, islet isolation, and microencapsulation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27738947/microencapsulation-in-clinical-islet-xenotransplantation
#7
Masayuki Shimoda, Shinichi Matsumoto
Allogeneic islet transplantation has become a viable treatment for patients with unstable type 1 diabetes; however, donor shortage and the necessity for immunosuppressive drugs are the major drawbacks of this approach. Microencapsulated porcine islet xenotransplantation could solve these drawbacks. Clinical porcine islet xenotransplantation as well as microencapsulated islet transplantation has been conducted without significant side effects. However, these transplantations are not as efficacious as allogeneic naked islet transplantation...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27738946/immunological-challenges-facing-translation-of-alginate-encapsulated-porcine-islet-xenotransplantation-to-human-clinical-trials
#8
Rahul Krishnan, David Ko, Clarence E Foster, Wendy Liu, A M Smink, Bart de Haan, Paul De Vos, Jonathan R T Lakey
Transplantation of alginate-encapsulated islets has the potential to treat patients suffering from type I diabetes, a condition characterized by an autoimmune attack against insulin-secreting beta cells. However, there are multiple immunological challenges associated with this procedure, all of which must be adequately addressed prior to translation from trials in small animal and nonhuman primate models to human clinical trials. Principal threats to graft viability include immune-mediated destruction triggered by immunogenic alginate impurities, unfavorable polymer composition and surface characteristics, and release of membrane-permeable antigens, as well as damage associated molecular patterns (DAMPs) by the encapsulated islets themselves...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27738935/a-method-of-porcine-pancreatic-islet-isolation-for-microencapsulation
#9
William F Kendall, Emmanuel C Opara
Since the discovery of insulin by Banting and Best in 1921, the prognosis and treatment options for individuals with diabetes have improved. The development of various insulin types, various oral agents, and insulin pumps have improved the available medical options for individuals afflicted with diabetes. The current need for frequent blood glucose monitoring imposed by multiple daily insulin injections, result in significant life-style challenges for in individuals afflicted with Type 1 diabetes (T1D). In contrast the use of surgical interventions, such as whole organ pancreas transplantation (PT) requires less-intensive glucose monitoring while the organ is viable...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27677911/induction-management-and-complications-of-streptozotocin-induced-diabetes-mellitus-in-rhesus-monkeys
#10
Jong-Min Kim, Jun-Seop Shin, Byoung-Hoon Min, Hyun-Je Kim, Jung-Sik Kim, Il-Hee Yoon, Won-Young Jeong, Ga-Eul Lee, Min-Sun Kim, Ju-Eun Kim, Sang-Man Jin, Chung-Gyu Park
BACKGROUND: Diabetes mellitus (DM) model using streptozotocin (STZ) which induces chemical ablation of β cell in the pancreas has been widely used for various research purposes in non-human primates. However, STZ has been known to have a variety of adverse effects such as nephrotoxicity, hepatotoxicity, and even mortality. The purpose of this study is to report DM induction by STZ, toxicity associated with STZ and procedure and complication of exogenous insulin treatment for DM management in rhesus monkeys (Macaca mulatta) that are expected to be transplanted with porcine islets within 2 months...
September 27, 2016: Xenotransplantation
https://www.readbyqxmd.com/read/27677465/no-perv-transmission-during-a-clinical-trial-of-pig-islet-cell-transplantation
#11
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/27633468/gene-editing-advance-re-ignites-debate-on-the-merits-and-risks-of-animal-to-human-transplantation
#12
R K F Fung, I H Kerridge
In Australia, and internationally, the shortage of organ and tissue donors significantly limits the number of patients with critical organ or tissue failure who are able to receive a transplant each year. The rationale for xenotransplantation - the transplantation of living cells, tissues or organs from one species to another - is to meet this shortfall in human donor material. While early clinical trials showed promise, particularly in patients with type I diabetes whose insulin dependence could be temporarily reversed by the transplantation of porcine islet cells, these benefits have been balanced with scientific, clinical and ethical concerns revolving around the risks of immune rejection and the potential transmission of porcine endogenous retroviruses or other infectious agents from porcine grafts to human recipients...
September 2016: Internal Medicine Journal
https://www.readbyqxmd.com/read/27592597/clinical-benefit-of-islet-xenotransplantation-for-the-treatment-of-type-1-diabetes
#13
Shinichi Matsumoto, Adrian Abalovich, Carlos Wechsler, Shaun Wynyard, Robert B Elliott
BACKGROUND: Allogeneic islet transplantation has become a viable option for the treatment of unstable type 1 diabetes. However, the donor shortage and the necessity of the immunosuppressive drugs are two major issues. To solve these issues, we performed islet xenotransplantation using encapsulated neonatal porcine islets without immunosuppressive drugs. METHODS: Two different doses (approximately 5000IEQ/kg and 10,000IEQ/kg) of encapsulated neonatal porcine islets were transplanted twice (total approximately 10,000IEQ/kg and 20,000IEQ/kg) into four type 1 diabetic patients in each group (total 8 patients)...
August 24, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27586421/pancreatic-islets-methods-for-isolation-and-purification-of-juvenile-and-adult-pig-islets
#14
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/27517501/genetic-strategies-to-bring-islet-xenotransplantation-to-the-clinic
#15
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/27500267/characterizing-the-mechanistic-pathways-of-the-instant-blood-mediated-inflammatory-reaction-in-xenogeneic-neonatal-islet-cell-transplantation
#16
David Liuwantara, Yi Vee Chew, Emmanuel J Favaloro, Joanne M Hawkes, Heather L Burns, Philip J O'Connell, Wayne J Hawthorne
INTRODUCTION: The instant blood-mediated inflammatory reaction (IBMIR) causes major loss of islets after transplantation and consequently represents the initial barrier to survival of porcine neonatal islet cell clusters (NICC) after xenotransplantation. METHODS: This study used novel assays designed to characterize the various immunologic components responsible for xenogeneic IBMIR to identify initiators and investigate processes of IBMIR-associated coagulation, complement activation and neutrophil infiltration...
June 2016: Transplantation Direct
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
#17
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/27440468/islet-cell-transplantation-from-g%C3%A3-ttingen-minipigs-to-cynomolgus-monkeys-analysis-of-virus-safety
#18
Vladimir A Morozov, Stefan Ludwig, Barbara Ludwig, Avi Rotem, Uriel Barkai, Stefan R Bornstein, Joachim Denner
BACKGROUND: Xenotransplantation using pig cells, tissues or organs may be associated with the transmission of porcine zoonotic micro-organisms. Hepatitis E virus (HEV), porcine cytomegalovirus (PCMV) and porcine endogenous retroviruses (PERVs) are potentially zoonotic micro-organisms which do not show clinical symptoms in pigs and which are due to the low expression level difficult to detect. Göttingen Minipigs (GöMP) are often used for biomedical investigations and they are well characterized concerning the presence of numerous bacteria, fungi, viruses and parasites and therefore may be used for islet cell transplantation...
July 2016: Xenotransplantation
https://www.readbyqxmd.com/read/27422454/islet-derived-damage-associated-molecular-pattern-molecule-contributes-to-immune-responses-following-microencapsulated-neonatal-porcine-islet-xenotransplantation-in%C3%A2-mice
#19
Takeshi Itoh, Yuko Hata, Hitomi Nishinakamura, Kenjiro Kumano, Hiroyuki Takahashi, Shohta Kodama
BACKGROUND: Clinical allogeneic islet transplantation has become an attractive procedure for type 1 diabetes mellitus treatment. However, there is a severe shortage of human donors. Microencapsulated neonatal porcine islet (NPI) xenotransplantation may be an alternative transplantation procedure. Currently, the efficacy of microencapsulated NPI xenotransplantation into the peritoneal cavity is limited because of early non-function resulting from inflammation, which is a serious hindrance to promoting this procedure as a standard therapy...
September 2016: Xenotransplantation
https://www.readbyqxmd.com/read/27387829/failure-of-transplantation-tolerance-induction-by-autologous-regulatory-t-cells-in-the-pig-to-non-human-primate-islet-xenotransplantation-model
#20
Jun-Seop Shin, Byoung-Hoon Min, Jong-Min Kim, Jung-Sik Kim, Il Hee Yoon, Hyun Je Kim, Yong-Hee Kim, Jae Yool Jang, Hee Jung Kang, Dong-Gyun Lim, Jongwon Ha, Sang-Joon Kim, Chung-Gyu Park
BACKGROUND: Islet allotransplantation is a promising way to treat some type 1 diabetic (T1D) patients with frequent hypoglycemic unawareness, and islet xenotransplantation is emerging to overcome the problem of donor organ shortage. Our recent study showing reproducible long-term survival of porcine islets in non-human primates (NHPs) allows us to examine whether autologous regulatory T-cell (Treg) infusion at peri-transplantation period would induce transplantation tolerance in xenotransplantation setting...
July 2016: Xenotransplantation
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