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https://www.readbyqxmd.com/read/29331269/clinical-benefits-of-autologous-haematopoietic-stem-cell-transplantation-in-type-1-diabetes-patients
#1
B Gu, H Miao, J Zhang, J Hu, W Zhou, W Gu, W Wang, G Ning
Type 1 diabetes (T1D) is characterized by severe damage to pancreas islet function through immunological attack; therefore, it is also called 'insulin-dependent diabetes'. The present study aimed to evaluate the safety and clinical efficacy of autologous haematopoietic stem cell transplantation (AHSCT) in adolescent patients with newly diagnosed T1D. A phase-II prospective, parallel-assignment, non-randomized trial was conducted from March 2008 to December 2011 with 40 T1D patients, of whom 20 received AHSCT therapy and 20 were treated only with insulin injections...
December 22, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29319179/muscle-derived-satellite-cells-for-treating-type-1-diabetes-in-rats-rattus-norvegicus
#2
Yu Ren, Hefei Wang, Si Ha, Xingsheng Zhao, Xiao Wang, Yu Lan, Xiaoling Liu
Diabetes mellitus(DM) is a complicated metabolic disease, with the fundamental treatment nowadays being diet control, insulin injections, slet or pancreas transplantation, which is limited because exogenous insulin injections fail to simulate normal insulin secretion in islet beta cells successfully and islet transplantation lacks organ donors. So far, stem cells with highly self-renewal and multi-directional differentiation potential have become a new hope for the treatment of diabetes. In this research, rat Muscle-derived satellite cells *MDSCs*were separated and cultivated in vitro and inducted into insulin-producing cells with observation and identification using dithizone staining and so on...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29315020/systematic-review-of-islet-cryopreservation
#3
Greg G Kojayan, Michael Alexander, David K Imagawa, Jonathan R T Lakey
Pancreatic islet transplantation is being extensively researched as an alternative treatment for type 1 diabetic patients. This treatment is currently limited by temporal mismatch, between the availability of pancreas and isolated islets from deceased organ donor, and the recipient's need for freshly isolated islets. To solve this issue, cryopreservation of islets may offer the potential to bank islets for transplant on demand. Cryopreservation, however, introduces an overwhelmingly harsh environment to the ever-so-fragile islets...
January 9, 2018: Islets
https://www.readbyqxmd.com/read/29311365/simultaneous-recognition-of-allogeneic-mhc-and-cognate-autoantigen-by-autoreactive-t-cells-in-transplant-rejection
#4
Adam L Burrack, Laurie G Landry, Janet Siebert, Marilyne Coulombe, Ronald G Gill, Maki Nakayama
The autoimmune condition is a primary obstacle to inducing tolerance in type 1 diabetes patients receiving allogeneic pancreas transplants. It is unknown how autoreactive T cells that recognize self-MHC molecules contribute to MHC-disparate allograft rejection. In this report, we show the presence and accumulation of dual-reactive, that is autoreactive and alloreactive, T cells in C3H islet allografts that were transplanted into autoimmune diabetic NOD mice. Using high-throughput sequencing, we discovered that T cells prevalent in allografts share identical TCRs with autoreactive T cells present in pancreatic islets...
January 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29306997/extracellular-matrix-molecules-and-their-potential-contribution-to-the-function-of-transplanted-pancreatic-islets
#5
REVIEW
L Alberto Llacua, Marijke M Faas, Paul de Vos
Extracellular matrix (ECM) molecules are responsible for structural and biochemical support, as well as for regulation of molecular signalling and tissue repair in many organ structures, including the pancreas. In pancreatic islets, collagen type IV and VI, and laminins are the most abundant molecules, but other ECM molecules are also present. The ECM interacts with specific combinations of integrin α/β heterodimers on islet cells and guides many cellular processes. More specifically, some ECM molecules are involved in beta cell survival, function and insulin production, while others can fine tune the susceptibility of islet cells to cytokines...
January 6, 2018: Diabetologia
https://www.readbyqxmd.com/read/29288549/transplantation-of-macro-encapsulated-human-islets-within-the-bioartificial-pancreas-%C3%AE-air-to-patients-with-type-1-diabetes-mellitus
#6
Per-Ola Carlsson, Daniel Espes, Amir Sedigh, Avi Rotem, Baruch Zimermann, Helena Grinberg, Tali Goldman, Uriel Barkai, Yuval Avni, Gunilla T Westermark, Lina Carlbom, Håkan Ahlström, Olof Eriksson, Johan Olerud, Olle Korsgren
Macroencapsulation devices provide the dual possibility to immunoprotect transplanted cells while also being retrievable; the latter bearing importance for safety in future trials with stem-cell derived cells. However, macroencapsulation entails a problem with oxygen supply to the encapsulated cells. The βAir device solves this with an incorporated refillable oxygen tank. This phase 1 study evaluated the safety and efficacy of implanting the βAir device containing allogeneic human pancreatic islets to patients with type 1 diabetes...
December 29, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29276781/recent-progress-in-the-use-and-tracking-of-transplanted-islets-as-a-personalized-treatment-for-type-1-diabetes
#7
Genaro A Paredes-Juarez, Paul de Vos, Jeff W M Bulte
Introduction: Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which the pancreas produces insufficient amounts of insulin. T1DM patients require exogenous sources of insulin to maintain euglycemia. Transplantation of naked or microencapsulated pancreatic islets represents an alternative paradigm to obtain an autonomous regulation of blood glucose levels in a controlled and personalized fashion. However, once transplanted, the fate of these personalized cellular therapeutics is largely unknown, justifying the development of non-invasive tracking techniques...
2017: Expert Review of Precision Medicine and Drug Development
https://www.readbyqxmd.com/read/29275427/hope-vs-hype-where-are-we-in-type-1-diabetes
#8
REVIEW
Jay S Skyler
Much progress has been made in type 1 diabetes research. Biological replacement of islet function has been achieved with pancreas transplantation and with islet transplantation. In the future, human embryonic stem cells and/or induced pluripotent stem cells may offer a potentially unlimited source of cells for islet replacement. Another potential strategy is to induce robust beta cell replication so that regeneration of islets can be achieved. Immune interventions are being studied with the hope of arresting the type 1 diabetes disease process to either prevent the disease or help preserve beta cell function...
December 23, 2017: Diabetologia
https://www.readbyqxmd.com/read/29259578/t-cell-mediated-beta-cell-destruction-autoimmunity-and-alloimmunity-in-the-context-of-type-1-diabetes
#9
REVIEW
Adam L Burrack, Tijana Martinov, Brian T Fife
Type 1 diabetes (T1D) results from destruction of pancreatic beta cells by T cells of the immune system. Despite improvements in insulin analogs and continuous blood glucose level monitoring, there is no cure for T1D, and some individuals develop life-threatening complications. Pancreas and islet transplantation have been attractive therapeutic approaches; however, transplants containing insulin-producing cells are vulnerable to both recurrent autoimmunity and conventional allograft rejection. Current immune suppression treatments subdue the immune system, but not without complications...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29251107/multicenter-assessment-of-animal-free-collagenase-af-1-for-human-islet-isolation
#10
Daniel Brandhorst, Géraldine Parnaud, Andrew Friberg, Vanessa Lavallard, Sandrine Demuylder-Mischler, Stephen Hughes, Julia Saphörster, Manfred Kurfürst, Olle Korsgren, Thierry Berney, Paul R V Johnson
Animal-free (AF) SERVA Collagenase AF-1 and Neutral Protease (NP) AF GMP Grade have recently become available for human islet isolation. This report describes the initial experiences of 3 different islet transplant centers. Thirty-four human pancreases were digested using 1 vial of the 6 different lots of Collagenase AF-1 (2,000-2,583 PZ-U/vial) supplemented with 4 different lots of NP AF in a range of 50 to 160 DMC-U per pancreas. Isolation, culture, and quality assessment were performed using standard techniques as previously described...
October 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29208633/in-vivo-visualization-of-beta-cells-by-targeting-of-gpr44
#11
Olof Eriksson, Peter Johnström, Zsolt Cselenyi, Mahabuba Jahan, Ram K Selvaraju, Marianne Jensen-Waern, Akihiro Takano, Maria Sörhede Winzell, Christer Halldin, Stanko Skrtic, Olle Korsgren
GPR44 expression has recently been described as highly beta cell selective in the human pancreas and constitutes a tentative surrogate imaging biomarker in diabetes.A radiolabeled small molecule GPR44 antagonist, [11C]AZ12204657, was evaluated for visualization of beta cells in pigs and non-human primates by Positron Emission Tomography (PET) as well as in immunodeficient mice transplanted with human islets under the kidney capsule. In vitro autoradiography of human and animal pancreatic sections from non-diabetic and diabetic subjects, in combination with insulin staining, was performed to assess beta cell selectivity of the radiotracer...
December 5, 2017: Diabetes
https://www.readbyqxmd.com/read/29160954/islet-allo-autotransplantation-allogeneic-pancreas-transplantation-followed-by-transplant-pancreatectomy-and-islet-transplantation
#12
M F Nijhoff, J Dubbeld, A R van Erkel, P J M van der Boog, T J Rabelink, M A Engelse, E J P de Koning
Simultaneous pancreas/kidney (SPK) transplantation is an important treatment option for patients with type 1 diabetes (T1D) and end stage renal disease (ESRD). Due to complications, in up to 10% of cases allograft pancreatectomy is necessary shortly after transplantation. Usually the donor pancreas is discarded. Here we report on a novel procedure to rescue endocrine tissue after allograft pancreatectomy. A 39-year-old woman with T1D and ESRD who had received an SPK transplantation required emergency allograft pancreatectomy due to bleeding at the vascular anastomosis...
November 21, 2017: American Journal of Transplantation
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
#13
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
#14
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
#15
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
#16
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
#17
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...
November 21, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/29048258/selection-of-implantation-sites-for-transplantation-of-encapsulated-pancreatic-islets
#18
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
#19
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
#20
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
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