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pancreas transplantation islets

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https://www.readbyqxmd.com/read/29140547/islet-transplantation-as-safe-and-efficacious-method-to-restore-glycemic-control-and-to-avoid-severe-hypoglycemia-after-donor-organ-failure-in-pancreas-transplantation
#1
Philipp A Gerber, Michel Hochuli, Bara D Benediktsdottir, Richard A Zuellig, Oliver Tschopp, Michael Glenck, Olivier de Rougemont, Christian Oberkofler, Giatgen A Spinas, Roger Lehmann
The aim of this study was to assess safety and efficacy of islet transplantation after initial pancreas transplantation with subsequent organ failure. Patients undergoing islet transplantation at our institution after pancreas organ failure were compared to a control group of patients with pancreas graft failure, but without islet transplantation and to a group receiving pancreas re-transplantation. 10 patients underwent islet transplantation after initial pancreas transplantation failed and were followed for a median of 51 months...
November 15, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/29123178/a-nanobody-based-tracer-targeting-dpp6-for-non-invasive-imaging-of-human-pancreatic-endocrine-cells
#2
Alexander Balhuizen, Sam Massa, Iris Mathijs, Jean-Valery Turatsinze, Jens De Vos, Stéphane Demine, Catarina Xavier, Olatz Villate, Isabelle Millard, Dominique Egrise, Carmen Capito, Raphaël Scharfmann, Pieter In't Veld, Piero Marchetti, Serge Muyldermans, Serge Goldman, Tony Lahoutte, Luc Bouwens, Decio L Eizirik, Nick Devoogdt
There are presently no reliable ways to quantify endocrine cell mass (ECM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. To address this unmet need, we coupled RNA sequencing of human pancreatic islets to a systems biology approach to identify new biomarkers of the endocrine pancreas. Dipeptidyl-Peptidase 6 (DPP6) was identified as a target whose mRNA expression is at least 25-fold higher in human pancreatic islets as compared to surrounding tissues and is not changed by proinflammatory cytokines...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29078330/favorable-outcome-of-experimental-islet-xenotransplantation-without-immunosuppression-in-a-nonhuman-primate-model-of-diabetes
#3
Barbara Ludwig, Stefan Ludwig, Anja Steffen, Yvonne Knauf, Baruch Zimerman, Sophie Heinke, Susann Lehmann, Undine Schubert, Janine Schmid, Martina Bleyer, Uwe Schönmann, Clark K Colton, Ezio Bonifacio, Michele Solimena, Andreas Reichel, Andrew V Schally, Avi Rotem, Uriel Barkai, Helena Grinberg-Rashi, Franz-Josef Kaup, Yuval Avni, Peter Jones, Stefan R Bornstein
Transplantation of pancreatic islets for treating type 1 diabetes is restricted to patients with critical metabolic lability resulting from the need for immunosuppression and the shortage of donor organs. To overcome these barriers, we developed a strategy to macroencapsulate islets from different sources that allow their survival and function without immunosuppression. Here we report successful and safe transplantation of porcine islets with a bioartificial pancreas device in diabetic primates without any immune suppression...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29073149/intrapancreatic-injection-of-human-bone-marrow-derived-mesenchymal-stem-stromal-cells-alleviates-hyperglycemia-and-modulates-the-macrophage-state-in-streptozotocin-induced-type-1-diabetic-mice
#4
Norimitsu Murai, Hirokazu Ohtaki, Jun Watanabe, Zhifang Xu, Shun Sasaki, Kazumichi Yagura, Seiji Shioda, Shoichiro Nagasaka, Kazuho Honda, Masahiko Izumizaki
Type 1 diabetes mellitus is a progressive disease caused by the destruction of pancreatic β-cells, resulting in insulin dependency and hyperglycemia. While transplanted bone marrow-derived mesenchymal stem/stromal cells (BMMSCs) have been explored as an alternative therapeutic approach for diseases, the choice of delivery route may be a critical factor determining their sustainability. This study evaluated the effects of intrapancreatic and intravenous injection of human BMMSCs (hBMMSCs) in streptozotocin (STZ)-induced type 1 diabetic mouse model...
2017: PloS One
https://www.readbyqxmd.com/read/29051963/applications-of-particulate-oxygen-generating-substances-pogs-in-the-bioartificial-pancreas
#5
John P McQuilling, Sivanandane Sittadjody, Samuel Pendergraft, Alan C Farney, Emmanuel C Opara
Type-1 Diabetes (T1D) is a devastating autoimmune disorder which results in the destruction of beta cells within the pancreas. A promising treatment strategy for T1D is the replacement of the lost beta cell mass through implantation of immune-isolated microencapsulated islets referred to as the bioartificial pancreas. The goal of this approach is to restore blood glucose regulation and prevent the long-term comorbidities of T1D without the need for immunosuppressants. A major requirement in the quest to achieve this goal is to address the oxygen needs of islet cells...
October 20, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/29048258/selection-of-implantation-sites-for-transplantation-of-encapsulated-pancreatic-islets
#6
Haitao Zhu, Wenjing Li, Zhongwei Liu, Wenliang Li, Niuniu Chen, Linlin Lu, Wei Zhang, Zhen Wang, Bo Wang, Kaili Pan, Xiaoge Zhang, Guoqiang Chen
Pancreatic islet transplantation has been validated as a valuable therapy for type 1 diabetes mellitus patients with exhausted insulin treatment. However, this therapy remains limited by the shortage of donor and the requirement of lifelong immunosuppression. Islet encapsulation, as an available bioartificial pancreas (BAP), represents a promising approach to enable protecting islet grafts without or with minimal immunosuppression and possibly expanding the donor pool. In order to develop a clinically implantable BAP, some key aspects need to be taken into accounts: encapsulation material, capsule design and implantation site...
October 19, 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/29029025/insulin-deficient-mouse-%C3%AE-cells-do-not-fully-mature-but-can-be-remedied-through-insulin-replacement-by-islet-transplantation
#7
Adam Ramzy, Majid Mojibian, Timothy J Kieffer
Insulin receptor insufficiency in β-cells leads to impaired insulin secretion and reduced β-cell hyperplasia in response to hyperglycemia. Selective insulin receptor deficiency in β-cells in later embryological development may lead to compensatory β-cell hyperplasia. Though these findings suggest insulin signaling on the β-cell is important for β-cell function, they are confounded by loss of signaling by the IGFs through the insulin receptor. To determine if insulin itself is necessary for β-cell development and maturation, we performed a characterization of pancreatic islets in mice with deletions of both non-allelic insulin genes (Ins1-/-Ins2-/-)...
September 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/29026874/australia-and-new-zealand-islets-and-pancreas-transplant-registry-annual-report-2017-pancreas-waiting-list-recipients-and-donors
#8
Angela C Webster, James Hedley, Abhijit Patekar, Paul Robertson, Patrick J Kelly
This is a registry report from the Australia and New Zealand Islet and Pancreas Transplant Registry. We report data for all solid organ pancreas transplant activity from inception in 1984 to end of 2016. Data analysis was performed using Stata Software version 14 (StataCorp, College Station, Tex). From 1984 to 2016 a total of 756 solid organ pancreas transplants have been performed in Australia and New Zealand, in 738 individuals. In 2016, 55 people received a pancreas transplant. These transplants were performed in Auckland (4), Monash (22), and Westmead (29)...
October 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28984038/beta-cell-replacement-strategies-for-diabetes
#9
Timothy J Kieffer, Knut Woltjen, Kenji Osafune, Daisuke Yabe, Nobuya Inagaki
Diabetes is characterized by elevated levels of blood glucose as a result of insufficient production of insulin from loss or dysfunction of pancreatic islet beta cells. Here we review several approaches to replace beta cells that were recently discussed at a symposium held in Kyoto, Japan. Transplant of donor human islets can effectively treat diabetes and eliminate the need for insulin injections, supporting research aimed at identifying abundant supplies of cells. Studies demonstrating the feasibility of producing mouse islets in rats support the concept of generating pigs with human pancreas that can serve as donors of human islets, although scientific and ethical challenges remain...
October 6, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28975176/deformability-based-microfluidic-separation-of-pancreatic-islets-from-exocrine-acinar-tissue-for-transplant-applications
#10
Walter B Varhue, Linda Langman, Molly Kelly-Goss, Morgan Lataillade, Kenneth L Brayman, Shayn Peirce-Cottler, Nathan S Swami
The long-term management of type-1 diabetes (T1D) is currently achieved through lifelong exogenous insulin injections. Although there is no cure for T1D, transplantation of pancreatic islets of Langerhans has the potential to restore normal endocrine function versus the morbidity of hypoglycemic unawareness that is commonly associated with sudden death among fragile diabetics. However, since endocrine islet tissues form a small proportion of the pancreas, sufficient islet numbers can be reached only by combining islets from multiple organ donors and the transplant plug contains significantly high levels of exocrine acinar tissue, thereby exacerbating immune responses...
October 25, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28964481/pediatric-pancreas-transplantation-including-total-pancreatectomy-with-islet-autotransplantation
#11
Alexander J Bondoc, Maisam Abu-El-Haija, Jaimie D Nathan
Unlike other solid-organ transplants, whole pancreas transplantation in children is relatively rare, and it occurs more frequently in the context of multivisceral or composite organ transplantation. Because children only infrequently suffer severe sequelae of type 1 diabetes mellitus, pancreas transplantation is rarely indicated in the pediatric population. More commonly, pediatric pancreas transplant occurs in the setting of incapacitating acute recurrent or chronic pancreatitis, specifically islet autotransplantation after total pancreatectomy...
August 2017: Seminars in Pediatric Surgery
https://www.readbyqxmd.com/read/28963457/kinetics-of-functional-beta-cell-mass-decay-in-a-diphtheria-toxin-receptor-mouse-model-of-diabetes
#12
Pim P van Krieken, Andrea Dicker, Maria Eriksson, Pedro L Herrera, Ulf Ahlgren, Per-Olof Berggren, Erwin Ilegems
Functional beta cell mass is an essential biomarker for the diagnosis and staging of diabetes. It has however proven technically challenging to study this parameter during diabetes progression. Here we have detailed the kinetics of the rapid decline in functional beta cell mass in the RIP-DTR mouse, a model of hyperglycemia resulting from diphtheria toxin induced beta cell ablation. A novel combination of imaging modalities was employed to study the pattern of beta cell destruction. Optical projection tomography of the pancreas and longitudinal in vivo confocal microscopy of islets transplanted into the anterior chamber of the eye allowed to investigate kinetics and tomographic location of beta cell mass decay in individual islets as well as at the entire islet population level...
September 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28951824/intraocular-in%C3%A2-vivo-imaging-of-pancreatic-islet-cell-physiology-pathology
#13
REVIEW
Ingo B Leibiger, Per-Olof Berggren
BACKGROUND: Diabetes mellitus has reached epidemic proportions and requires new strategies for treatment. Unfortunately, the efficacy of treatment regimens on maintaining/re-gaining functional beta cell mass can, at the present, only be determined indirectly. Direct monitoring of beta cell mass is complicated by the anatomy of the endocrine pancreas, which consists of thousands to a million of discrete micro-organs, i.e. islets of Langerhans, which are scattered throughout the pancreas...
September 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28885496/%C3%A3-cell-replacement-therapy-the-next-10-years
#14
Christian Schuetz, Takayuki Anazawa, Sarah E Cross, Leticia Labriola, Raphael P H Meier, Robert R Redfield, Hanne Scholz, Peter G Stock, Nathan W Zammit
ß cell replacement with either pancreas or islet transplantation has progressed immensely over the last decades with current 1- and 5-year insulin independence rates of ~85% and ~50%, respectively. Recent advances are largely attributed to improvements in immunosuppressive regimen, donor selection and surgical technique. However, both strategies are compromised by a scarce donor source. Xenotransplantation provides a potential solution by providing a theoretically unlimited supply of islets, but clinical application has been limited by concerns for a potent immune response against xenogeneic tissue...
September 6, 2017: Transplantation
https://www.readbyqxmd.com/read/28870071/orcein-related-small-molecule-o4-destabilizes-hiapp-protofibrils-by-interacting-mostly-with-the-amyloidogenic-core-region
#15
Yu Zou, Zhenyu Qian, Yunxiang Sun, Guanghong Wei, Qingwen Zhang
The accumulation of the human islet amyloid polypeptide (hIAPP) deposits in the pancreas is regarded as an important factor that leads to the depletion of islet β-cells and islet transplantation failure. In recent experiments, it was reported that a small organic molecule O4 inhibits the formation of hIAPP1-37 oligomers and fibrils. However, the interaction between O4 molecules and hIAPP oligomers is largely unknown on the atomic level. In this work, we studied the influence of O4 molecules on fibril-like hIAPP pentamer and decamer by performing atomistic molecular dynamics simulations...
September 22, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28854965/adipose-stem-cells-from-chronic-pancreatitis-patients-improve-mouse-and-human-islet-survival-and-function
#16
Lili Song, Zhen Sun, Do-Sung Kim, Wenyu Gou, Charlie Strange, Huansheng Dong, Wanxing Cui, Gary Gilkeson, Katherine A Morgan, David B Adams, Hongjun Wang
BACKGROUND: Chronic pancreatitis has surgical options including total pancreatectomy to control pain. To avoid surgical diabetes, the explanted pancreas can have islets harvested and transplanted. Immediately following total pancreatectomy with islet autotransplantation (TP-IAT), many islet cells die due to isolation and transplantation stresses. The percentage of patients remaining insulin free after TP-IAT is therefore low. We determined whether cotransplantation of adipose-derived mesenchymal stem cells (ASCs) from chronic pancreatitis patients (CP-ASCs) would protect islets after transplantation...
August 30, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28843156/small-molecule-at7867-proliferates-pdx1-expressing-pancreatic-progenitor-cells-derived-from-human-pluripotent-stem-cells
#17
Azuma Kimura, Taro Toyoda, Yohei Nishi, Makoto Nasu, Akira Ohta, Kenji Osafune
While pancreatic islet transplantation achieves insulin independence in type 1 diabetes (T1D) patients, its widespread application is limited by donor tissue scarcity. Pancreatic progenitor cells (PPCs) give rise to all cell types in the pancreas during development. PPCs derived from human pluripotent stem cells have been shown to differentiate into functional β cells both in vitro and in vivo, and to reverse hyperglycemia, at least in mice. Therefore, PPCs have great potential to serve as an alternative cell source for cell therapy, and the identification of compounds that facilitate PPC proliferation could provide stable and large-scale pancreatic cell preparation systems in clinical settings...
August 17, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28835662/pancreatic-islet-macroencapsulation-using-microwell-porous-membranes
#18
Katarzyna Skrzypek, Milou Groot Nibbelink, Jéré van Lente, Mijke Buitinga, Marten A Engelse, Eelco J P de Koning, Marcel Karperien, Aart van Apeldoorn, Dimitrios Stamatialis
Allogeneic islet transplantation into the liver in combination with immune suppressive drug therapy is widely regarded as a potential cure for type 1 diabetes. However, the intrahepatic system is suboptimal as the concentration of drugs and nutrients there is higher compared to pancreas, which negatively affects islet function. Islet encapsulation within semipermeable membranes is a promising strategy that allows for the islet transplantation outside the suboptimal liver portal system and provides environment, where islets can perform their endocrine function...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28835141/transplantation-of-stromal-derived-factor-1%C3%AE-and-basic-fibroblast-growth-factor-primed-insulin-producing-cells-reverses-hyperglycaemia-in-diabetic-rats
#19
Muhammad Sohail Anjum, Azra Mehmood, Muhammad Ali, Hira Butt, Shaheen N Khan, Sheikh Riazuddin
The defective insulin production is associated with severely reduced islet cell mass leading to diabetes. Growth factors preconditioned stem cells have arisen as an effective therapy to treat many diseases including diabetes. The current study was designed to assess the effect of pretreatment of ASCs derived IPCs with combination of stromal cell derived factor 1 alpha (SDF1α) and basic fibroblast growth factor (bFGF) in improving glucose tolerance in streptozotocin induced diabetic rats. The results showed maximally significant reduction in hyperglycaemia and fibrosis, while up-regulation of survival and pancreas-specific genes, insulin levels and homing of transplanted cells in SDF-1α + bFGF IPCs transplanted rats as compared with other groups...
August 24, 2017: Growth Factors
https://www.readbyqxmd.com/read/28832685/oxygen-environment-and-islet-size-are-the-primary-limiting-factors-of-isolated-pancreatic-islet-survival
#20
Hirotake Komatsu, Colin Cook, Chia-Hao Wang, Leonard Medrano, Henry Lin, Fouad Kandeel, Yu-Chong Tai, Yoko Mullen
BACKGROUND: Type 1 diabetes is an autoimmune disease that destroys insulin-producing beta cells in the pancreas. Pancreatic islet transplantation could be an effective treatment option for type 1 diabetes once several issues are resolved, including donor shortage, prevention of islet necrosis and loss in pre- and post-transplantation, and optimization of immunosuppression. This study seeks to determine the cause of necrotic loss of isolated islets to improve transplant efficiency. METHODOLOGY: The oxygen tension inside isolated human islets of different sizes was simulated under varying oxygen environments using a computational in silico model...
2017: PloS One
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