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Islet transplant

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https://www.readbyqxmd.com/read/28226413/thrombalexin-use-of-a-cytotopic-anticoagulant-to-reduce-thrombotic-microangiopathy-in-a-highly-sensitized-model-of-kidney-transplantation
#1
Miriam Manook, Jean Kwun, Christian Burghuber, Kannan Samy, Michael Mulvihill, Janghoon Yoon, He Xu, Andrea L MacDonald, Kyle Freischlag, Verna Curfman, Evelyn Branum, David Howell, Alton Brad Farris, Richard A Smith, Stephen Sacks, Anthony Dorling, Nizam Mamode, Stuart Knechtle
Early activation of coagulation is an important factor in the initiation of innate immunity, as characterized by thrombotic microangiopathy (TMA). In transplantation, systemic anti-coagulation is difficult due to bleeding. A novel 'cytotopic' agent, 'Thrombalexin', (TLN) combines a cell-membrane bound (mirystoyl tail) anti-thrombin (HLL peptide) which can be perfused directly to the donor organ or cells.. Thromboelastography (TEG) was used to measure time to clot formation (r-time) in both rhesus and human blood, comparing TLN vs...
February 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28222054/ucp2-expression-is-increased-in-pancreas-from-brain-dead-donors-and-involved-in-cytokine-induced-%C3%AE-cells-apoptosis
#2
Leticia A Brondani, Tatiana H Rech, Gabriela Boelter, Andrea C Bauer, Cristiane B Leitão, Décio L Eizirik, Daisy Crispim
BACKGROUND: Systemic inflammation associated with brain death (BD) decreases islet yield and quality, negatively affecting outcomes of human islet transplantation. A recent study from our group showed an increased expression of uncoupling protein-2 (UCP2) in pancreas from rats with BD as compared with controls. UCP2 is located in the mitochondrial inner membrane and regulates production of reactive oxygen species and glucose-stimulated insulin secretion. It has been suggested that UCP2 also plays a role in β cell apoptosis, but these findings remain controversial...
March 2017: Transplantation
https://www.readbyqxmd.com/read/28219959/randomised-prospective-medico-economic-nationwide-french-study-of-islet-transplantation-in-patients-with-severely-unstable-type-1-diabetes-the-stabilot-study-protocol
#3
Sandrine Lablanche, Sandra David-Tchouda, Jennifer Margier, Edith Schir, Anne Wojtusciszyn, Sophie Borot, Laurence Kessler, Emmanuel Morelon, Charles Thivolet, François Pattou, Marie Christine Vantyghem, Thierry Berney, Pierre-Yves Benhamou
INTRODUCTION: Islet transplantation may be an appropriate treatment option for patients with severely unstable type 1 diabetes experiencing major glucose variability with severe hypoglycaemia despite intensive insulin therapy. Few data are available on the costs associated with islet transplantation in relation to its benefits. The STABILOT study proposes to assess the economic impact of islet transplantation in comparison with the current best medical treatment defined as sensor-augmented pump (SAP) therapy...
February 20, 2017: BMJ Open
https://www.readbyqxmd.com/read/28207637/the-efficacy-of-a-prevascularized-retrievable-poly-d-l-lactide-co-%C3%AE%C2%B5-caprolactone-subcutaneous-scaffold-as-transplantation-site-for-pancreatic-islets
#4
Alexandra M Smink, Shiri Li, Don T Hertsig, Bart J de Haan, Leendert Schwab, Aart A van Apeldoorn, Eelco de Koning, Marijke M Faas, Jonathan R T Lakey, Paul de Vos
BACKGROUND: The liver as transplantation site for human pancreatic islets is a harsh microenvironment for islets and it lacks the ability to retrieve the graft. A retrievable, extrahepatic transplantation site that mimics the pancreatic environment is desired. Ideally this transplantation site should be located subdermal for easy surgical-access but this never resulted in normoglycemia. Here we describe the design and efficacy of a novel prevascularized, subcutaneously implanted, retrievable poly (D,L-lactide-co-ε-caprolactone) (PDLLCL) scaffold...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28201960/hypoglycemia-and-glucocorticoid-free-immunosuppression-are-related-with-low-dehydroepiandrosterone-sulfate-level
#5
Martina Zahradnicka, Frantisek Saudek, Kvetoslav Lipar, Jelena Skibova
BACKGROUND: Low dehydroepiandrosterone sulfate (DHEAS) levels and a high cortisol/DHEAS ratio are associated with higher mortality in elderly, dialyzed, and immunocompromised patients. The role of these hormones in patients with hypoglycemia unawareness (hypo) or in pancreas or islet recipients treated by glucocorticoid-free immunosuppressive regimen (IS) has not been studied. OBJECTIVE: The aim of this study was to determine the effects of IS and of recurrent hypoglycemia on DHEAS and adrenocorticotropic hormone (ACTH) levels in patients with type-1 diabetes (T1DM)...
February 13, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28188872/pre-transplantation-31-p-magnetic-resonance-spectroscopy-for-quality-assessment-of-human-pancreatic-grafts-a-feasibility-study
#6
Lina Carlbom, Jan Weis, Lars Johansson, Olle Korsgren, Håkan Ahlström
OBJECTIVE: To investigate the feasibility of using (31)P-MRS for objective non-invasive quality assessment of human pancreas grafts prior to transplantation or islet isolation. MATERIALS AND METHODS: Pancreata from 5 human donors, 3 males and 2 females, aged 49-78years, with body mass index (BMI) 22-31kg/m(2), were included. Pancreata were perfused with histidine-tryptophan-ketoglutarate solution during procurement and stored in hypothermic condition (4°C) for 21-44h...
February 8, 2017: Magnetic Resonance Imaging
https://www.readbyqxmd.com/read/28186705/current-and-future-perspectives-on-alginate-encapsulated-pancreatic-islet
#7
Berit L Strand, Abba E Coron, Gudmund Skjak-Braek
Transplantation of pancreatic islets in immune protective capsules holds the promise as a functional cure for type 1 diabetes, also about 40 years after the first proof of principal study. The concept is simple in using semipermeable capsules that allow the ingress of oxygen and nutrients, but limit the access of the immune system. Encapsulated human islets have been evaluated in four small clinical trials where the procedure has been evaluated as safe, but lacking long-term efficacy. Host reactions toward the biomaterials used in the capsules may be one parameter limiting the long-term function of the graft in humans...
February 2, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28174675/comparison-of-purification-solutions-with-different-osmolality-for-porcine-islet-purification
#8
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
#9
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/28174291/local-sphingosine-kinase-1-activity-improves-islet-transplantation
#10
Darling Rojas-Canales, Daniella Penko, Kay K Myo Min, Kate A Parham, Heshan Peiris, Rainer V Haberberger, Stuart M Pitson, Chris Drogemuller, Damien J Keating, Shane T Grey, Patrick T Coates, Claudine S Bonder, Claire F Jessup
Pancreatic islet transplantation is a promising clinical treatment for type I diabetes (T1D), but success is limited by extensive beta cell death in the immediate post-transplant period, and impaired islet function in the longer term. Following transplantation, appropriate vascular remodelling is crucial to ensure the survival and function of engrafted islets. The sphingosine kinase pathway is an important regulator of vascular beds, but its role in the survival and function of transplanted islets is unknown...
February 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28169284/long-term-glycemic-control-in-adult-patients-undergoing-remote-vs-local-total-pancreatectomy-with-islet-autotransplantation
#11
Samuel J Kesseli, Matthew Wagar, Min K Jung, Kerrington D Smith, Yu Kuei Lin, R Matthew Walsh, Betul Hatipoglu, Martin L Freeman, Timothy L Pruett, Gregory J Beilman, David E R Sutherland, Ty B Dunn, David A Axelrod, Sushela S Chaidarun, Tyler K Stevens, Melena Bellin, Timothy B Gardner
OBJECTIVES: Total pancreatectomy with islet autotransplantation (TPIAT) is increasingly performed with remote islet cell processing and preparation, i.e., with islet cell isolation performed remotely from the primary surgical site at an appropriately equipped islet isolation facility. We aimed to determine whether TPIAT using remote islet isolation results in comparable long-term glycemic outcomes compared with TPIAT performed with standard local isolation. METHODS: We performed a retrospective cohort study of adult patients who underwent TPIAT at three tertiary care centers from 2010 to 2013...
February 7, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28151049/effect-of-co-culture-of-mesenchymal-stem-stromal-cells-with-pancreatic-islets-on-viability-and-function-outcomes-a-systematic-review-and-meta-analysis
#12
Bianca Marmontel de Souza, Ana Paula Bouças, Fernanda Dos Santos de Oliveira, Karina Pires Reis, Patrícia Ziegelmann, Andrea Carla Bauer, Daisy Crispim
The maintenance of viable and functional pancreatic islets is crucial for successful islet transplantation from brain-dead donors. To overcome islet quality loss during culture, some studies have co-cultured islets with mesenchymal stem/stromal cells (MSC). However, it is still uncertain if MSC-secreted factors are enough to improve islet quality or if a physical contact between MSCs and islets is needed. Therefore, we performed a systematic review and meta-analysis to clarify the effect of different culture contact systems of islets with MSCs on viability and insulin secretion outcomes...
February 2, 2017: Islets
https://www.readbyqxmd.com/read/28150744/engineering-an-endocrine-neo-pancreas-by-repopulation-of-a-decellularized-rat-pancreas-with-islets-of-langerhans
#13
H Napierala, K-H Hillebrandt, N Haep, P Tang, M Tintemann, J Gassner, M Noesser, H Everwien, N Seiffert, M Kluge, E Teegen, D Polenz, S Lippert, D Geisel, A Reutzel Selke, N Raschzok, A Andreou, J Pratschke, I M Sauer, B Struecker
Decellularization of pancreata and repopulation of these non-immunogenic matrices with islets and endothelial cells could provide transplantable, endocrine Neo- Pancreata. In this study, rat pancreata were perfusion decellularized and repopulated with intact islets, comparing three perfusion routes (Artery, Portal Vein, Pancreatic Duct). Decellularization effectively removed all cellular components but conserved the pancreas specific extracellular matrix. Digital subtraction angiography of the matrices showed a conserved integrity of the decellularized vascular system but a contrast emersion into the parenchyma via the decellularized pancreatic duct...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28142500/hyaluronic-acid-collagen-hydrogel-as-an-alternative-to-alginate-for-long-term-immunoprotected-islet-transplantation
#14
Stephen Harrington, S Janette Williams, Sonia Rawal, Karthik Ramachandran, Lisa Stehno-Bittel
Alginate has long been the material of choice for immunoprotection of islets for its low cost and ability to easily form microspheres. Unfortunately, this seaweed-derived material is notoriously prone to fibrotic overgrowth in vivo, resulting in premature graft failure. The purpose of this study was to test an alternative, hyaluronic acid (HA-COL), for in vitro function, viability and allogeneic islet transplant outcomes in diabetic rats. In vitro studies indicated that the HA-COL gel had diffusion characteristics that would allow small molecules like glucose and insulin to enter and exit the gel, while larger molecules (70 and 500kD dextrans) were impeded from diffusing past the gel edge in 24 hours...
January 31, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28135283/the-spleen-is-an-ideal-site-for-inducing-transplanted-islet-graft-expansion-in-mice
#15
Takeshi Itoh, Hitomi Nishinakamura, Kenjiro Kumano, Hiroyuki Takahashi, Shohta Kodama
Alternative islet transplantation sites have the potential to reduce the marginal number of islets required to ameliorate hyperglycemia in recipients with diabetes. Previously, we reported that T cell leukemia homeobox 1 (Tlx1)+ stem cells in the spleen effectively regenerated into insulin-producing cells in the pancreas of non-obese diabetic mice with end-stage disease. Thus, we investigated the spleen as a potential alternative islet transplantation site. Streptozotocin-induced diabetic C57BL/6 mice received syngeneic islets into the portal vein (PV), beneath the kidney capsule (KC), or into the spleen (SP)...
2017: PloS One
https://www.readbyqxmd.com/read/28130881/transplantation-of-hepatocytes-from-genetically-engineered-pigs-into-baboons
#16
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
#17
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/28127888/insulin-delivery-to-the-brain-using-intracranial-implantation-of-alginate-encapsulated-pancreatic-islets
#18
Konstantin Bloch, Alexey Vanichkin, Irit Gil-Ad, Pnina Vardi, Abraham Weizman
There is increasing evidence supporting a link between cognitive dysfunctions and impaired brain insulin signalling. Insulin therapy has previously been tested as an approach to ameliorate brain insulin resistance and deficiency in patients with various brain disorders. However, current strategies for insulin delivery to the brain may induce severe hypoglycaemia when injected peripherally or show poor uptake when delivered intranasally. Recently, we have shown that intracranial transplantation of naked pancreatic islets increased insulin content in the brain and attenuated cognitive dysfunctions without altering peripheral glucose homeostasis in rats with schizophrenia-like syndrome...
January 27, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28126963/plasma-derived-proteomic-biomarkers-in-hla-haploidentical-or-hla-matched-bone-marrow-transplantation-using-post-transplantation-cyclophosphamide
#19
Christopher G Kanakry, Giorgos Bakoyannis, Susan M Perkins, Shannon R McCurdy, Ante Vulic, Edus H Warren, Etienne Daguindau, Taylor Olmsted, Christen Mumaw, Andrea M H Towlerton, Kenneth R Cooke, Paul V O'Donnell, Heather J Symons, Sophie Paczesny, Leo Luznik
Recent studies have suggested that plasma-derived proteins may be potential biomarkers relevant for graft-versus-host disease and/or non-relapse mortality occurring after allogeneic blood or marrow transplantation. However, none of these putative biomarkers have been assessed in patients treated either with HLA-haploidentical blood or marrow transplantation or with post-transplantation cyclophosphamide, which has been repeatedly associated with low rates of severe acute graft-versus-host disease, chronic graft-versus-host disease, and non-relapse mortality...
January 25, 2017: Haematologica
https://www.readbyqxmd.com/read/28117444/interspecies-organogenesis-generates-autologous-functional-islets
#20
Tomoyuki Yamaguchi, Hideyuki Sato, Megumi Kato-Itoh, Teppei Goto, Hiromasa Hara, Makoto Sanbo, Naoaki Mizuno, Toshihiro Kobayashi, Ayaka Yanagida, Ayumi Umino, Yasunori Ota, Sanae Hamanaka, Hideki Masaki, Sheikh Tamir Rashid, Masumi Hirabayashi, Hiromitsu Nakauchi
Islet transplantation is an established therapy for diabetes. We have previously shown that rat pancreata can be created from rat pluripotent stem cells (PSCs) in mice through interspecies blastocyst complementation. Although they were functional and composed of rat-derived cells, the resulting pancreata were of mouse size, rendering them insufficient for isolating the numbers of islets required to treat diabetes in a rat model. Here, by performing the reverse experiment, injecting mouse PSCs into Pdx-1-deficient rat blastocysts, we generated rat-sized pancreata composed of mouse-PSC-derived cells...
February 9, 2017: Nature
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