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Islet transplantation

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https://www.readbyqxmd.com/read/29338388/novel-fusion-protein-targeting-mitochondrial-dna-improves-pancreatic-islet-functional-potency-and-islet-transplantation-outcomes
#1
Juan S Danobeitia, Peter J Chlebeck, Inna Shokolenko, Xiaobo Ma, Glenn Wilson, Luis A Fernandez
Long-term graft survival is an ongoing challenge in the field of islet transplantation. With the growing demand for transplantable organs, therapies to improve organ quality and reduce the incidence of graft dysfunction are of paramount importance. We evaluated the protective role of a recombinant DNA repair protein targeted to mitochondria (Exscien I-III), as a therapeutic agent using a rodent model of pancreatic islet transplantation. We first investigated the effect of therapy on isolated rat islets cultured with pro-inflammatory cytokines (interleukin-1 β, interferon γ, and tumor necrosis factor α) for 48 h and documented a significant reduction in apoptosis by flow cytometry, improved viability by immunofluorescence, and conserved functional potency in vitro and in vivo in Exscien I-III-treated islets...
November 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29338381/effect-of-the-diabetic-state-on-islet-engraftment-and-function-in-a-large-animal-model-of-islet-kidney-transplantation
#2
Prashanth Vallabhajosyula, Atsushi Hirakata, Matthew Weiss, Adam Griesemer, Akira Shimizu, Hanzhou Hong, Andreas Habertheuer, Vaja Tchipashvili, Kazuhiko Yamada, David H Sachs
In islet transplantation, in addition to immunologic and ischemic factors, the diabetic/hyperglycemic state of the recipient has been proposed, although not yet validated, as a possible cause of islet toxicity, contributing to islet loss during the engraftment period. Using a miniature swine model of islet transplantation, we have now assessed the effect of a persistent state of hyperglycemia on islet engraftment and subsequent function. An islet-kidney (IK) model previously described by our laboratory was utilized...
November 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29337308/rage-binds-preamyloid-iapp-intermediates-and-mediates-pancreatic-%C3%AE-cell-proteotoxicity
#3
Andisheh Abedini, Ping Cao, Annette Plesner, Jinghua Zhang, Meilun He, Julia Derk, Sachi A Patil, Rosa Rosario, Jacqueline Lonier, Fei Song, Hyunwook Koh, Huilin Li, Daniel P Raleigh, Ann Marie Schmidt
Islet amyloidosis is characterized by the aberrant accumulation of islet amyloid polypeptide (IAPP) in pancreatic islets, resulting in β cell toxicity, which exacerbates type 2 diabetes and islet transplant failure. It is not fully clear how IAPP induces cellular stress or how IAPP-induced toxicity can be prevented or treated. We recently defined the properties of toxic IAPP species. Here, we have identified a receptor-mediated mechanism of islet amyloidosis-induced proteotoxicity. In human diabetic pancreas and in cellular and mouse models of islet amyloidosis, increased expression of the receptor for advanced glycation endproducts (RAGE) correlated with human IAPP-induced (h-IAPP-induced) β cell and islet inflammation, toxicity, and apoptosis...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29333922/effect-of-resveratrol-treatment-on-graft-revascularization-after-islet-transplantation-in-streptozotocin-induced-diabetic-mice
#4
Eun-Mi Lee, Inwon Park, Ye-Jee Lee, Young-Hye You, Ji-Won Kim, Myung-Jun Kim, Yu-Bae Ahn, Pilhan Kim, Seung-Hyun Ko
We evaluated the effect of resveratrol (RSV) on graft survival after islet transplantation (ITx) in diabetic mice. Isolated islets from Balb/c mice (200 IEQ) were transplanted under the kidney capsule of diabetic Balb/c mice. Vehicle or RSV (200 mg/kg/day, orally) was given for 14 days after ITx. Two more control groups [STZ-treated (No-ITx-Control) and STZ+RSV-treated (No-ITx-RSV) mice without ITx] were added. Glucose tolerance tests (GTT) was performed at 14 days after ITx. In vitro, isolated islets pretreated with vehicle or RSV (1 μM) were incubated in a hypoxic chamber (O2 1%, 1hr)...
January 15, 2018: Islets
https://www.readbyqxmd.com/read/29331269/clinical-benefits-of-autologous-haematopoietic-stem-cell-transplantation-in-type-1-diabetes-patients
#5
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/29330944/improvement-of-islet-function-and-survival-by-integration-of-perfluorodecalin-into-microcapsules-in-vivo-and-in-vitro
#6
Sang-Ho Lee, Heon-Seok Park, Yeoree Yang, Eun-Young Lee, Ji-Won Kim, Gilson Khang, Kun-Ho Yoon
Hypoxic injury of islets is a major obstacle for encapsulated islet transplantation into the peritoneal cavity. To improve oxygen delivery to encapsulated islets, we integrated 20% of the oxygen carrier material, perfluorodecalin (PFD), in alginate capsules mixed with islets (PFD-alginate). Integration of PFD clearly improved islet viability and decreased reactive oxygen species production compared to islets encapsulated with alginate only (alginate) and naked islets exposed to hypoxia in vitro. In PFD-alginate capsules, HIF-1α expression was minimal, and insulin expression was well maintained...
January 12, 2018: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29330151/interleukin-22-reverses-human-islet-dysfunction-and-apoptosis-triggered-by-hyperglycemia-and-light
#7
Shadab Abadpour, Bente Halvorsen, Afaf Sahraoui, Olle Korsgren, Pål Aukrust, Hanne Scholz
Interleukin (IL)-22 has recently been suggested as an anti-inflammatory cytokine that could protect the islet cells from inflammation- and glucose-induced toxicity. We have previously shown that the tumor necrosis factor family member, LIGHT can impair human islet function at least partly via pro-apoptotic effects. Herein, we aimed to investigate the protective role of IL-22 on human islets exposed to the combination of hyperglycemia and LIGHT. First, we found up-regulation of LIGHT receptors (LTβR and HVEM) in engrafted human islets exposed to hyperglycemia (>11 mM) for 17 days post transplantation by using a double islet transplantation mouse model as well as in human islets cultured with high glucose (HG) (20mM glucose) + LIGHT in vitro and this latter effect was attenuated by IL-22...
January 12, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29329189/beta-cell-death-by-cell-free-dna-and-outcome-after-clinical-islet-transplantation
#8
Boris L Gala-Lopez, Daniel Neiman, Tatsuya Kin, Doug O'Gorman, Andrew R Pepper, Andrew J Malcolm, Sheina Pianzin, Peter A Senior, Patricia Campbell, Benjamin Glaser, Yuval Dor, Ruth Shemer, A M James Shapiro
BACKGROUND: Optimizing engraftment and early survival after clinical islet transplantation is critical to long-term function, but there are no reliable, quantifiable measures to assess beta cell death. Circulating cell free DNA (cfDNA) derived from beta cells has been identified as a novel biomarker to detect cell loss, and was recently validated in new-onset type 1 diabetes and in islet transplant patients. METHODS: Herein we report beta cell cfDNA measurements after allotransplantation in 37 subjects and the correlation with clinical outcomes...
January 11, 2018: Transplantation
https://www.readbyqxmd.com/read/29322561/effect-of-an-oxygen-generating-scaffold-on-the-viability-and-insulin-secretion-function-of-porcine-neonatal-pancreatic-cell-clusters
#9
Eun Mi Lee, Ji-In Jung, Zahid Alam, Hee-Gyeong Yi, Heejin Kim, Jin Woo Choi, Sunghoon Hurh, Young June Kim, Jong Cheol Jeong, Jaeseok Yang, Kook-Hwan Oh, Hee Chan Kim, Byeong Chun Lee, Inho Choi, Dong-Woo Cho, Curie Ahn
BACKGROUND: Islet encapsulation techniques have shown limited success in maintaining islet survival and function because encapsulation decreases oxygen supply. In this study, an oxygen-generating scaffold was fabricated to prevent hypoxic cell damage and improve the viability and insulin secretion of islets. METHODS: We fabricated an oxygen-generating scaffold by mixing calcium peroxide (CaO2 ) with polydimethylsiloxane (PDMS). We evaluated the effects of the oxygen-generating PDMS + CaO2 scaffold on viability, caspase-3 and caspase-7 activity, oxygen consumption rate (OCR), glucose-stimulated insulin secretion (GSIS), hypoxic cell marker expression, and reactive oxygen species (ROS) levels in porcine neonatal pancreatic cell clusters (NPCCs)...
January 10, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29320716/distinct-roles-of-systemic-and-local-actions-of-insulin-on-pancreatic-%C3%AE-cells
#10
Takumi Kitamoto, Kenichi Sakurai, Eun Young Lee, Koutaro Yokote, Domenico Accili, Takashi Miki
OBJECTIVE: Pancreatic β-cell mass and function are critical in glucose homeostasis. Their regulatory mechanisms have been studied principally under experimental conditions of reduced β-cell numbers, such as β-cell ablation and partial pancreatectomy. In the present study, we generated an opposite mouse model with an excessive amount of ectopic β-cells, and analyzed its consequence on β-cell mass and survival. METHODS: Mice underwent sub-renal transplantation (SRT) of pseudo-islets generated from a pancreatic β-cell line MIN6 or intra-pancreatic transplantation (IPT) of MIN6 cells, and morphological and functional changes of their endocrine pancreata were analyzed...
January 7, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29319810/the-second-phase-of-insulin-secretion-in-non-diabetic-islet-grafted-recipients-is-altered-and-can-predict-graft-outcome
#11
Orianne Villard, Jean Frédéric Brun, Lisa Bories, Nicolas Molinari, Pierre Yves Benhamou, Thierry Berney, Anne Wojtusciszyn
INTRODUCTION: Islet transplantation (IT) can treat patients with severely unstable type 1 diabetes. Pre-hepatic kinetics of insulin-secretion (ISec) in two phases can be calculated by C-peptide levels during meal tests. We propose to describe insulin secretion profile after a Mixed-Meal Tolerance Test (MMTT) in IT patients and to determine whether the calculated indexes of ISec can predict graft outcome. METHODS: We analyzed 34 MMTT among 11 patients who received an IT between 2011 and 2016 and compared them to healthy controls (C) and type 2 diabetic (T2D) patients...
January 8, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29319179/muscle-derived-satellite-cells-for-treating-type-1-diabetes-in-rats-rattus-norvegicus
#12
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
#13
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
#14
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/29309990/ex-vivo-generation-of-drug-eluting-islets-improves-transplant-outcomes-by-inhibiting-tlr4-mediated-nfkb-upregulation
#15
Charles A Chang, Babatope Akinbobuyi, Jeremy M Quintana, Gumpei Yoshimatsu, Bashoo Naziruddin, Robert R Kane
The systemic administration of immunosuppressive and anti-inflammatory drugs is routinely employed in organ transplantation to minimize graft rejection and improve graft survival. Localized drug delivery has the potential to improve transplant outcomes by providing sustained exposure to efficacious drug concentrations while avoiding systemic immunosuppression and off-target effects. Here, we describe the synthesis of a novel prodrug and its direct covalent conjugation to pancreatic islets via a cleavable linker...
December 28, 2017: Biomaterials
https://www.readbyqxmd.com/read/29307512/the-endoc-%C3%AE-h1-cell-line-is-a-valid-model-of-human-beta-cells-and-applicable-for-screenings-to-identify-novel-drug-target-candidates
#16
Violeta Georgieva Tsonkova, Fredrik Wolfhagen Sand, Xenia Asbæk Wolf, Lars Groth Grunnet, Anna Kirstine Ringgaard, Camilla Ingvorsen, Louise Winkel, Mark Kalisz, Kevin Dalgaard, Christine Bruun, Johannes Josef Fels, Charlotte Helgstrand, Sven Hastrup, Fredrik Kryh Öberg, Erik Vernet, Michael Paolo Bastner Sandrini, Allan Christian Shaw, Carsten Jessen, Mads Grønborg, Jacob Hald, Hanni Willenbrock, Dennis Madsen, Rasmus Wernersson, Lena Hansson, Jan Nygaard Jensen, Annette Plesner, Tomas Alanentalo, Maja Borup Kjær Petersen, Anne Grapin-Botton, Christian Honoré, Jonas Ahnfelt-Rønne, Jacob Hecksher-Sørensen, Philippe Ravassard, Ole D Madsen, Claude Rescan, Thomas Frogne
OBJECTIVE: To characterize the EndoC-βH1 cell line as a model for human beta cells and evaluate its beta cell functionality, focusing on insulin secretion, proliferation, apoptosis and ER stress, with the objective to assess its potential as a screening platform for identification of novel anti-diabetic drug candidates. METHODS: EndoC-βH1 was transplanted into mice for validation of in vivo functionality. Insulin secretion was evaluated in cells cultured as monolayer and as pseudoislets, as well as in diabetic mice...
December 19, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29307170/islet-transplantation-promotes-podocyte-regeneration-in-a-model-of-diabetic-nephropathy
#17
Ziqiang Xu, Jie Fan
Background/aim: The purpose of this study was to observe whether islet transplantation could induce glomerular parietal epithelial cells to express podocyte proteins in a rat model of streptozotocin-induced diabetic nephropathy (DN).Materials and methods: A total of 18 rats were given single injections of streptozotocin to induce a DN model. Eight weeks after the modeling, successfully established DN rats were divided into three groups: an untreated group (DN group), an islet-transplanted group (IT group), and an insulin group (IN group)...
December 19, 2017: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/29306997/extracellular-matrix-molecules-and-their-potential-contribution-to-the-function-of-transplanted-pancreatic-islets
#18
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/29304344/endogenous-reprogramming-of-alpha-cells-into-beta-cells-induced-by-viral-gene-therapy-reverses-autoimmune-diabetes
#19
Xiangwei Xiao, Ping Guo, Chiyo Shiota, Ting Zhang, Gina M Coudriet, Shane Fischbach, Krishna Prasadan, Joseph Fusco, Sabarinathan Ramachandran, Piotr Witkowski, Jon D Piganelli, George K Gittes
Successful strategies for treating type 1 diabetes need to restore the function of pancreatic beta cells that are destroyed by the immune system and overcome further destruction of insulin-producing cells. Here, we infused adeno-associated virus carrying Pdx1 and MafA expression cassettes through the pancreatic duct to reprogram alpha cells into functional beta cells and normalized blood glucose in both beta cell-toxin-induced diabetic mice and in autoimmune non-obese diabetic (NOD) mice. The euglycemia in toxin-induced diabetic mice and new insulin+ cells persisted in the autoimmune NOD mice for 4 months prior to reestablishment of autoimmune diabetes...
January 4, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29303357/the-synergy-of-two-factors-on-insulin-expression
#20
Ying Luo, Yao Xu, Zhen-Yu Wang, Xi Li, Wei-Bing Xing, Tong-Cun Zhang
As a potential cure for diabetes, more and more attentions have been paid to organ transplants to replace insulin therapy. As a result, many researchers have explored out many programs to get insulin-producing cells (IPCs) to replace the defective β cells. Currently, more and more new induction methods are being proposed, and at the same time, more and more possible induction molecular mechanisms are being revealed. The purpose of this study was to explore whether and how the two factors pdx-1 and myocardin affected the differentiation of rat mesenchymal stem cells (rMSCs) into IPCs...
January 5, 2018: Cellular Reprogramming
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