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https://www.readbyqxmd.com/read/28513004/effects-of-encapsulated-porcine-islets-on-glucose-and-c-peptide-concentrations-in-diabetic-nude-mice-6%C3%A2-months-after%C3%A2-intraperitoneal-transplantation
#1
Masuhiro Nishimura, Naho Iizuka, Yasutaka Fujita, Osamu Sawamoto, Shinichi Matsumoto
BACKGROUND: In patients with type 1 diabetes, allogeneic islet transplantation can provide normal HbA1c concentrations, but it requires immunosuppression. Transplanting encapsulated islets into the peritoneal cavity could reduce or eliminate the need for immunosuppression. One of the uncertain features of intraperitoneal islet transplantation is the difficulty of measuring C-peptide concentrations in peripheral blood, which is often used for the marker of islet function. We hypothesized that secreted C-peptide from intraperitoneally transplanted islets was mostly consumed in the peritoneal cavity, which resulted in low C-peptide concentrations in peripheral blood...
May 16, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28444910/characterization-of-porcine-endogenous-retrovirus-expression-in-neonatal-and-adult-pig-pancreatic-islets
#2
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/28426078/an-intravascular-bioartificial-pancreas-device-ibap-with-silicon-nanopore-membranes-snm-for-islet-encapsulation-under-convective-mass-transport
#3
Shang Song, Charles Blaha, Willieford Moses, Jaehyun Park, Nathan Wright, Joey Groszek, William Fissell, Shant Vartanian, Andrew M Posselt, Shuvo Roy
Diffusion-based bioartificial pancreas (BAP) devices are limited by poor islet viability and functionality due to inadequate mass transfer resulting in islet hypoxia and delayed glucose-insulin kinetics. While intravascular ultrafiltration-based BAP devices possess enhanced glucose-insulin kinetics, the polymer membranes used in these devices provide inadequate ultrafiltrate flow rates and result in excessive thrombosis. Here, we report the silicon nanopore membrane (SNM), which exhibits a greater hydraulic permeability and a superior pore size selectivity compared to polymer membranes for use in BAP applications...
May 16, 2017: Lab on a Chip
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
#4
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
#5
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/28324008/vessel-network-architecture-of-adult-human-islets-promotes-distinct-cell-cell-interactions-in-situ-and-is-altered-after-transplantation
#6
Christian M Cohrs, Chunguang Chen, Stephan R Jahn, Julia Stertmann, Helena Chmelova, Jürgen Weitz, Andrea Bähr, Nikolai Klymiuk, Anja Steffen, Barbara Ludwig, Virginia Kamvissi, Eckhard Wolf, Stefan R Bornstein, Michele Solimena, Stephan Speier
Islet cell hormone release is modulated by signals from endothelial and endocrine cells within the islet. However, models of intra-islet vascularization and paracrine cell signaling are mostly based on rodent pancreas. We here assessed for the first time the architecture and endocrine cell interaction of the vascular network in unperturbed human islets in situ and their potential to re-establish their endogenous vascular network after transplantation in vivo. We prepared pancreas tissue slices of fresh tissue obtained from non-diabetic patients undergoing partial pancreatectomy...
January 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28322428/xenotransplantation-where-do-we-stand-in-2016
#7
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
#8
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/28266040/ex-vivo-porcine-organ-perfusion-models-as-a-suitable-platform-for-translational-transplant-research
#9
Rohan Kumar, Wen Yuan Chung, Ashley Robert Dennison, Giuseppe Garcea
In transplantation surgery, extending the criteria for organ donation to include organs that may have otherwise been previously discarded has provided the impetus to improve organ preservation. The traditional method of cold static storage (CS) has been tried and tested and is suitable for organs meeting standard criteria donation. Ex vivo machine perfusion is, however, associated with evidence suggesting that it may be better than CS alone and may allow for organ donation criteria to be extended. Much of our knowledge of organ preservation is derived from animal studies...
March 6, 2017: Artificial Organs
https://www.readbyqxmd.com/read/28258588/gastrostomy-tube-placement-for-long-term-oral-drug-administration-in-non-human-primates
#10
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/28253305/chitosan-assisted-differentiation-of-porcine-adipose-tissue-derived-stem-cells-into-glucose-responsive-insulin-secreting-clusters
#11
Hui-Yu Liu, Chih-Chien Chen, Yuan-Yu Lin, Yu-Jen Chen, Bing-Hsien Liu, Shiu-Chung Wong, Cheng-Yu Wu, Yun-Tsui Chang, Han-Yi E Chou, Shih-Torng Ding
The unique advantage of easy access and abundance make the adipose-derived stem cells (ADSCs) a promising system of multipotent cells for transplantation and regenerative medicine. Among the available sources, porcine ADSCs (pADSCs) deserve especial attention due to the close resemblance of human and porcine physiology, as well as for the upcoming availability of humanized porcine models. Here, we report on the isolation and conversion of pADSCs into glucose-responsive insulin-secreting cells. We used the stromal-vascular fraction of the dorsal subcutaneous adipose from 9-day-old male piglets to isolate pADSCs, and subjected the cells to an induction scheme for differentiation on chitosan-coated plates...
2017: PloS One
https://www.readbyqxmd.com/read/28247506/the-effect-of-hypoxia-on-free-and-encapsulated-adult-porcine-islets-an-in-vitro-study
#12
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/28246290/co-transplantation-of-mesenchymal-stem-cells-with-neonatal-porcine-islets-improve-graft-function-in-diabetic-mice
#13
Julie A Hayward, Cara E Ellis, Karen Seeberger, Timothy Lee, Bassem Salama, Aillette Mulet-Sierra, Purushothaman Kuppan, Adetola Adesida, Gregory S Korbutt
Mesenchymal stem cells (MSCs) possess immuno-regulatory, anti-inflammatory, and pro-angiogenic properties, and therefore have the potential to improve islet engraftment and survival. We assessed the effect human bone marrow derived MSCs have on neonatal porcine islets (NPIs) in vitro and determine islet engraftment and metabolic outcomes when co-transplanted in a mouse model. NPIs co-cultured with MSCs had greater cellular insulin content and increased glucose stimulate insulin secretion. NPIs were co-transplanted with or without MSCs in diabetic B6...
February 28, 2017: Diabetes
https://www.readbyqxmd.com/read/28226413/thrombalexin-use-of-a-cytotopic-anticoagulant-to-reduce-thrombotic-microangiopathy-in-a-highly-sensitized-model-of-kidney-transplantation
#14
M Manook, J Kwun, C Burghuber, K Samy, M Mulvihill, J Yoon, H Xu, A L MacDonald, K Freischlag, V Curfman, E Branum, D Howell, A B Farris, R A Smith, S Sacks, A Dorling, N Mamode, S J Knechtle
Early activation of coagulation is an important factor in the initiation of innate immunity, as characterized by thrombotic microangiopathy (TMA). In transplantation, systemic anticoagulation is difficult due to bleeding. A novel "cytotopic" agent, thrombalexin (TLN), combines a cell-membrane-bound (myristoyl tail) anti-thrombin (hirudin-like peptide [HLL]), which can be perfused directly to the donor organ or cells. Thromboelastography was used to measure time to clot formation (r-time) in both rhesus and human blood, comparing TLN versus HLL (without cytotopic tail) versus negative control...
February 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28174675/comparison-of-purification-solutions-with-different-osmolality-for-porcine-islet-purification
#15
Chika Miyagi-Shiohira, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Yasufumi Noguchi, Masayuki Matsushita, Hirofumi Noguchi
The osmolality of the purification solution is one of the most critical variables in human islet purification during islet isolation. We previously reported the effectiveness of a combined continuous density/osmolality gradient for the supplemental purification of human islets. We herein applied a combined continuous density/osmolality gradient for regular purification. The islets were purified with a continuous density gradient without osmolality preparation [continuous density/normal osmolality (CD/NO)] or continuous density/osmolality solution with osmolality preparation by 10× Hank's balanced salt solution (HBSS) [continuous density/continuous osmolality (CD/CO)]...
January 8, 2017: Cell Medicine
https://www.readbyqxmd.com/read/28174674/the-evaluation-of-islet-purification-methods-that-use-large-bottles-to-create-a-continuous-density-gradient
#16
Chika Miyagi-Shiohira, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Yasufumi Noguchi, Masayuki Matsushita, Hirofumi Noguchi
Islet purification is one of the most important steps of islet isolation for pancreatic islet transplantation. The most common method of islet purification is density gradient centrifugation using a COBE 2991 cell processor. However, this method can damage islets mechanically through its high shearing force. We recently reported that a new purification method using large plastic bottles effectively achieves a high yield of islets from the porcine pancreas. In the present study, we evaluated the methods of making a continuous density gradient...
January 8, 2017: Cell Medicine
https://www.readbyqxmd.com/read/28130881/transplantation-of-hepatocytes-from-genetically-engineered-pigs-into-baboons
#17
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/28130838/production-of-high-quality-islets-from-goettingen-minipigs-choice-of-organ-preservation-solution-donor-pool-and-optimal-cold-ischemia-time
#18
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/28058735/safe-use-of-anti-cd154-monoclonal-antibody-in-pig-islet-xenotransplantation-in-monkeys
#19
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
#20
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
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