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Islet transplantation

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https://www.readbyqxmd.com/read/27916274/long-term-gaba-administration-induces-alpha-cell-mediated-beta-like-cell-neogenesis
#1
Nouha Ben-Othman, Andhira Vieira, Monica Courtney, Fabien Record, Elisabet Gjernes, Fabio Avolio, Biljana Hadzic, Noémie Druelle, Tiziana Napolitano, Sergi Navarro-Sanz, Serena Silvano, Keith Al-Hasani, Anja Pfeifer, Sandra Lacas-Gervais, Gunter Leuckx, Laura Marroquí, Julien Thévenet, Ole Dragsbaek Madsen, Decio Laks Eizirik, Harry Heimberg, Julie Kerr-Conte, François Pattou, Ahmed Mansouri, Patrick Collombat
The recent discovery that genetically modified α cells can regenerate and convert into β-like cells in vivo holds great promise for diabetes research. However, to eventually translate these findings to human, it is crucial to discover compounds with similar activities. Herein, we report the identification of GABA as an inducer of α-to-β-like cell conversion in vivo. This conversion induces α cell replacement mechanisms through the mobilization of duct-lining precursor cells that adopt an α cell identity prior to being converted into β-like cells, solely upon sustained GABA exposure...
November 18, 2016: Cell
https://www.readbyqxmd.com/read/27915019/the-impact-of-cell-surface-pegylation-and-short-course-immunotherapy-on-islet-graft-survival-in-an-allogeneic-murine-model
#2
Jaime A Giraldo, R Damaris Molano, Hernán R Rengifo, Carmen Fotino, Kerim M Gattás-Asfura, Antonello Pileggi, Cherie L Stabler
: Islet transplantation is a promising therapy for Type 1 diabetes mellitus; however, host inflammatory and immune responses lead to islet dysfunction and destruction, despite potent systemic immunosuppression. Grafting of poly(ethylene glycol) (PEG) to the periphery of cells or tissues can mitigate inflammation and immune recognition via generation of a steric barrier. Herein, we sought to evaluate the complementary impact of islet PEGylation with a short-course immunotherapy on the survival of fully-MHC mismatched islet allografts (DBA/2 islets into diabetic C57BL/6J recipients)...
November 30, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27914923/alloantigen-gene-transfer-to-hepatocytes-promotes-tolerance-to-pancreatic-islet-graft-by-inducing-cd8-regulatory-t-cells
#3
Valentin Le Guen, Jean-Paul Judor, Françoise Boeffard, Vanessa Gauttier, Nicolas Ferry, Jean-Paul Soulillou, Sophie Brouard, Sophie Conchon
BACKGROUND & AIM: Induction of donor-specific immune tolerance is a good alternative to chronic life-long immunosuppression for transplant patients. Donor major histocompatibility complex (MHC) molecules represent the main targets of the allogeneic immune response of transplant recipients. Liver-targeted gene transfer with viral vectors induces tolerance toward the encoded antigen. The aim of this work was to determine whether alloantigen gene transfer to hepatocytes induces tolerance and promotes graft acceptance...
November 30, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27909715/a-new-scaffold-containing-small-intestinal-submucosa-and-mesenchymal-stem-cells-improves-pancreatic-islet-function-and-survival-in%C3%A2-vitro-and-in%C3%A2-vivo
#4
Dan Wang, Xiaoming Ding, Wujun Xue, Jin Zheng, Xiaohui Tian, Yang Li, Xiaohong Wang, Huanjin Song, Hua Liu, Xiaohui Luo
It is unknown whether a scaffold containing both small intestinal submucosa (SIS) and mesenchymal stem cells (MSCs) for transplantation may improve pancreatic islet function and survival. In this study, we examined the effects of a SIS-MSC scaffold on islet function and survival in vitro and in vivo. MSCs and pancreatic islets were isolated from Sprague-Dawley rats, and SIS was isolated from Bamei pigs. The islets were apportioned among 3 experimental groups as follows: SIS-islets, SIS-MSC-islets and control-islets...
November 29, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27905403/infusion-with-human-bone-marrow-derived-mesenchymal-stem-cells-improves-%C3%AE-cell-function-in-patients-and-non-obese-mice-with-severe-diabetes
#5
Lirong Li, Hui Hui, Xiaolei Jia, Jie Zhang, Ying Liu, Qianyue Xu, Dalong Zhu
Mesenchymal stem cells (MSCs) transplantation is a promising therapeutic strategy for type 1 diabetes (T1D). However, little is known on whether MSC transplantation can benefit T1D patients with ketoacidosis and its potential actions. Here, we show that infusion with bone marrow MSCs preserves β-cell function in some T1D patients with ketoacidosis by decreasing exogenous insulin requirement and increasing plasma C-peptide levels up to 1-2 years. MSC transplantation increased plasma and islet insulin contents in non-obese diabetic (NOD) mice with severe diabetes...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895821/implanting-1-1b4-human-%C3%AE-cell-pseudoislets-improves-glycaemic-control-in-diabetic-severe-combined-immune-deficient-mice
#6
Alastair D Green, Srividya Vasu, Neville H McClenaghan, Peter R Flatt
AIM: To investigate the potential of implanting pseudoislets formed from human insulin-releasing β-cell lines as an alternative to islet transplantation. METHODS: In this study, the anti-diabetic potential of novel human insulin releasing 1.1B4 β-cells was evaluated by implanting the cells, either as free cell suspensions, or as three-dimensional pseudoislets, into the subscapular region of severe combined immune deficient mice rendered diabetic by single high-dose administration of streptozotocin...
November 15, 2016: World Journal of Diabetes
https://www.readbyqxmd.com/read/27893617/differential-role-of-b-cells-and-il-17-versus-ifn-%C3%AE-during-early-and-late-rejection-of-pig-islet-xenografts-in-mice
#7
Hee Kap Kang, Shusen Wang, Anil Dangi, Xiaomin Zhang, Amar Singh, Lei Zhang, James M Rosati, Wilma Suarez-Pinzon, Xuelian Deng, Xiaoyan Chen, Edward B Thorp, Bernhard J Hering, Stephen D Miller, Xunrong Luo
BACKGROUND: Xenogeneic islet transplantation is an emerging therapeutic option for diabetic patients. However, immunological tolerance to xenogeneic islets remains a challenge. METHODS: The current study used a pig-to-mouse discordant xenogeneic islet transplant model to examine anti-donor xenogeneic immune responses during early and late rejection, and to determine experimental therapeutic interventions that promote durable pig islet xenograft survival. RESULTS: We found that during early acute rejection of pig islet xenografts, the rejecting hosts exhibited a heavy graft infiltration with B220 B cells and a robust anti-pig antibody production...
November 23, 2016: Transplantation
https://www.readbyqxmd.com/read/27878382/ultra-marathon-100%C3%A2-km-in-an-islet-transplanted-runner
#8
Roberto Codella, Michela Adamo, Paola Maffi, Lorenzo Piemonti, Antonio Secchi, Livio Luzi
No abstract text is available yet for this article.
November 23, 2016: Acta Diabetologica
https://www.readbyqxmd.com/read/27872862/oxygenation-of-the-intraportally-transplanted-pancreatic-islet
#9
Thomas M Suszynski, Efstathios S Avgoustiniatos, Klearchos K Papas
Intraportal islet transplantation (IT) is not widely utilized as a treatment for type 1 diabetes. Oxygenation of the intraportally transplanted islet has not been studied extensively. We present a diffusion-reaction model that predicts the presence of an anoxic core and a larger partly functional core within intraportally transplanted islets. Four variables were studied: islet diameter, islet fractional viability, external oxygen partial pressure (P) (in surrounding portal blood), and presence or absence of a thrombus on the islet surface...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27872471/recent-progress-in-xenotransplantation-with-emphasis-on-virological-safety
#10
Joachim Denner
Xenotransplantation is a new technology that may help to overcome the shortage of human tissues and organs available for the treatment of tissue and organ failure. Remarkable progress has recently been made in this field. First, understanding of the mechanisms of immunological rejection, mainly of the hyperacute rejection, allowed generating numerous genetically modified pigs to overcome rejection. Second, based on these genetically modified animals and new immunosuppression regimens, long-term survival of non-human primate recipients of heart, kidney, and islet cell cells has been reported...
November 22, 2016: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/27870552/glycemic-predictors-of-insulin-independence-after-total-pancreatectomy-with-islet-auto-transplantation
#11
Michael Quartuccio, Erica Hall, Vikesh Singh, Martin A Makary, Kenzo Hirose, Niraj Desai, Christi Walsh, Daniel Warren, Zhaoli Sun, Ellen Stein, Rita R Kalyani
CONTEXT: Total pancreatectomy with islet auto transplantation (TPIAT) is a treatment for medically refractory chronic pancreatitis that can prevent postsurgical diabetes in a subset of patients. Predictors of insulin independence are needed for appropriate patient selection and counseling. OBJECTIVE: To explore glycemic predictors of insulin independence after TPIAT. DESIGN: A prospective cohort of patients undergoing TPIAT from 2011-2016...
November 21, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27865779/impairment-of-neurovascular-coupling-in-type-1-diabetes-mellitus-in-rats-is-prevented-by-pancreatic-islet-transplantation-and-reversed-by-a-semi-selective-pkc-inhibitor
#12
Francesco Vetri, Meirigeng Qi, Haoliang Xu, Jose Oberholzer, Chanannait Paisansathan
Streptozotocin (STZ)-induced chronic hyperglycemia has a detrimental effect on neurovascular coupling, linked to increased PKC-mediated phosphorylation and PKC isoform expression changes. Here, we sought to determine whether: 1) selective PKC-α/β/γ inhibitor, GF109203X, could reverse the effects of chronic hyperglycemia on cerebrovascular reactivity; 2) pancreatic islet transplantation could prevent the development of cerebrovascular impairment seen in a rat model of Type 1 Diabetes. We studied the effect of GF109203X in diabetic (DM), non-diabetic (ND), and transplanted (TR) Lewis rats during either sciatic nerve stimulation (SNS) or the topical applications of the large-conductance Ca(2+)-operated K(+) (BKCa) channel opener, NS1619, or the K(+) inward rectifier (Kir) channel agonist, KCl...
November 16, 2016: Brain Research
https://www.readbyqxmd.com/read/27862341/cost-and-clinical-outcome-of-islet-transplantation-in-norway-2010-2015
#13
Simen W Schive, Aksel Foss, Afaf Sahraoui, Kristine Kloster-Jensen, Geir Hafsahl, Gunnar Kvalheim, Torbjørn Lundgren, Bengt von Zur-Mühlen, Marie Felldin, Ehab Rafael, Marko Lempinen, Olle Korsgren, Trond G Jenssen, Vinod Mishra, Hanne Scholz
Islet transplantation is a minimally invasive β-cell replacement strategy. Islet transplantation is a reimbursed treatment in Norway. Here we summarize the cost and clinical outcome of 31 islet transplantations performed at Oslo University Hospital (OUS) from Januray 2010 - June 2015. Patients were retrospectively divided into 3 groups. 13 patients received either one or two islet transplantation alone (ITA), while 5 patients received islet transplantation after previous solid organ transplantation. For the group receiving 2 ITA, Kaplan-Meier estimates show an insulin independence of 20% more than 4 years after their last transplantation...
November 16, 2016: Clinical Transplantation
https://www.readbyqxmd.com/read/27861845/quantum-dots-labelling-allows-detection-of-the-homing-of-mesenchymal-stem-cells-administered-as-immunomodulatory-therapy-in-an-experimental-model-of-pancreatic-islets-transplantation
#14
Silvia Mannucci, Laura Calderan, Paola Quaranta, Sara Antonini, Franco Mosca, Biancamaria Longoni, Pasquina Marzola, Federico Boschi
Cell transplantation is considered a promising therapeutic approach in several pathologies but still needs innovative and non-invasive imaging technologies to be validated. The use of mesenchymal stem cells (MSCs) attracts major interest in clinical transplantation thanks to their regenerative properties, low immunogenicity and ability to regulate immune responses. In several animal models, MSCs are used in co-transplantation with pancreatic islets (PIs) for the treatment of type I diabetes, supporting graft survival and prolonging normal glycaemia levels...
November 15, 2016: Journal of Anatomy
https://www.readbyqxmd.com/read/27853630/current-stem-cell-based-therapies-in-diabetes
#15
REVIEW
Meredith A Lilly, Meghan F Davis, Josh E Fabie, Elizabeth B Terhune, G Ian Gallicano
Diabetes is a disease with wide-ranging personal and societal impacts that has been managed medicinally for over half a century. Since the discovery of stem cells, pancreatic islet regeneration has become a central target for clinical application that has the potential to decrease or eliminate the need for insulin administration and adjunctive medications. The discovery of alternative routes to pluripotency that bypass the ethical implications of embryonic stem cells has significantly expanded the horizons of stem cell based therapy...
2016: American Journal of Stem Cells
https://www.readbyqxmd.com/read/27853629/current-progress-of-human-trials-using-stem-cell-therapy-as-a-treatment-for-diabetes-mellitus
#16
REVIEW
Shuk Kei Cheng, Elisse Y Park, Andjela Pehar, Alexandra C Rooney, G Ian Gallicano
Diabetes mellitus affects millions of people worldwide, and is associated with serious complications that affect nearly all body systems. Because of the severity of this global health concern, there is a great deal of research being performed on alternative treatments and possible cures. Previous treatments for diabetes have included exogenous insulin injection and pancreatic islet transplantations. These treatment methods have several limitations; thus, the use of stem cells in treating diabetes is currently a significant area of research...
2016: American Journal of Stem Cells
https://www.readbyqxmd.com/read/27851902/therapeutic-potential-of-mesenchymal-stem-cells-for-the-treatment-of-diabetic-peripheral-neuropathy
#17
Marianna Monfrini, Elisabetta Donzelli, Virginia Rodriguez-Menendez, Elisa Ballarini, Valentina Alda Carozzi, Alessia Chiorazzi, Cristina Meregalli, Annalisa Canta, Norberto Oggioni, Luca Crippa, Federica Avezza, Sara Silvani, Barbara Bonandrini, Marina Figliuzzi, Andrea Remuzzi, Carla Porretta-Serapiglia, Roberto Bianchi, Giuseppe Lauria, Giovanni Tredici, Guido Cavaletti, Arianna Scuteri
Type-1 Diabetes is generally treated with exogenous insulin administration. Despite treatment, a very common long term consequence of diabetes is the development of a disabling and painful peripheral neuropathy. The transplantation of pancreatic islets is an advanced alternative therapeutic approach, but its clinical application is still very limited, mainly because of the great number of islets required to complete the procedure and of their short-term survival. An intriguing method to improve the performance of pancreatic islets transplantation is the co-transplantation of Mesenchymal Stem Cells (MSCs), adult stem cells already known to support the survival of different cellular populations...
November 13, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27846404/local-release-of-dexamethasone-from-macroporous-scaffolds-accelerates-islet-transplant-engraftment-by-promotion-of-anti-inflammatory-m2-macrophages
#18
Kaiyuan Jiang, Jessica D Weaver, Yangjunyi Li, Xiongjian Chen, Jiapu Liang, Cherie L Stabler
Transplant-associated inflammatory responses generate an unfavorable microenvironment for tissue engraftment, particularly for cells susceptible to inflammatory stress, such as pancreatic islets. The localized delivery of anti-inflammatory agents, such as glucocorticoids, offers a promising approach to minimize the detrimental side effects associated with systemic delivery; however, the dosage must be carefully tailored to avoid deleterious responses, such as poor engraftment. Herein, we employed a polydimethylsiloxane (PDMS)-based three-dimensional scaffold platform for the local and controlled delivery of dexamethasone (Dex)...
November 5, 2016: Biomaterials
https://www.readbyqxmd.com/read/27843954/continuous-quadrupole-magnetic-separation-of-islets-during-digestion-improves-purified-porcine-islet-viability
#19
Bradley P Weegman, Venkata Sunil Kumar Sajja, Thomas M Suszynski, Michael D Rizzari, William E Scott Iii, Jennifer P Kitzmann, Kate R Mueller, Thomas R Hanley, David J Kennedy, Paul W Todd, Appakalai N Balamurugan, Bernhard J Hering, Klearchos K Papas
Islet transplantation (ITx) is an emerging and promising therapy for patients with uncontrolled type 1 diabetes. The islet isolation and purification processes require exposure to extended cold ischemia, warm-enzymatic digestion, mechanical agitation, and use of damaging chemicals for density gradient separation (DG), all of which reduce viable islet yield. In this paper, we describe initial proof-of-concept studies exploring quadrupole magnetic separation (QMS) of islets as an alternative to DG to reduce exposure to these harsh conditions...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27842980/establishment-characterization-and-long-term-culture-of-human-endocrine-pancreas-derived-microvascular-endothelial-cells
#20
Valeria Sordi, Anna Ferri, Valentina Ceserani, Emilio Ciusani, Erica Dugnani, Silvia Pellegrini, Rita Nano, Lorenza Pecciarini, Augusto Pessina, Luisa Pascucci, Lorenzo Piemonti, Giulio Alessandri
BACKGROUND: In vitro primary cultures of microvascular endothelial cells from endocrine pancreas are difficult to obtain, but can be a very helpful tool for studies of islet biology, transplantation and regenerative medicine. METHODS: We applied a protocol recently described for the isolation and culture of brain microvascular endothelial cells (EC) on human pancreatic islets. EC obtained were characterized in terms of morphological (light and transmission electron microscopy), phenotypical (by immunofluorescence and flow cytometry) and functional (cord formation assay and protein secretion by multiplex bead-based assay) characteristics...
November 11, 2016: Cytotherapy
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