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Islet transplantation

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https://www.readbyqxmd.com/read/28101160/facile-mechanical-shaking-method-is-an-improved-isolation-approach-for-islet-preparation-and-transplantation
#1
Nina Yin, Tao Chen, Yuling Yu, Yongming Han, Fei Yan, Zhou Zheng, Zebin Chen
Successful islet isolation is crucial for islet transplantation and cell treatment for type 1 diabetes. Current isolation methods are able to obtain 500-1,000 islets per rat, which results in a waste of ≥50% of total islets. In the present study, a facile mechanical shaking method for improving islet yield (up to 1,500 per rat) was developed and summarized, which was demonstrated to be more effective than the existing well-established stationary method. The present results showed that isolated islets have a maximum yield of 1,326±152 when shaking for 15 min for the fully-cannulated pancreas...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28098405/shielding-engineered-islets-with-mesenchymal-stem-cells-enhance-survival-under-hypoxia
#2
Bhawna Chandravanshi, Ramesh Ramchandra Bhonde
In the present study we focused on the improvisation of islet survival in hypoxia.The Islet like cell aggregates (ICAs) derived from wharton's jelly mesenchymal stem cells (WJ MSC) were cultured with and without WJ MSC for 48h in hypoxia and normoxia and tested for their direct trophic effect on β cell survival. The WJ MSCs themselves secreted insulin upon glucose challenge and expressed the pancreatic markers at both transcription and translational level (C-peptide, Insulin,Glucagon and Glut 2). Direct contact of MSCs with ICAs facilitated highest viability under hypoxia as evidenced by fluorescein diacetate/propidium iodide and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay...
January 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28078385/glucose-and-fatty-acids-synergistically-and-reversibly-promote-beta-cell-proliferation-in-rats
#3
Valentine S Moullé, Kevin Vivot, Caroline Tremblay, Bader Zarrouki, Julien Ghislain, Vincent Poitout
AIMS/HYPOTHESIS: The mechanisms underlying pancreatic islet mass expansion have attracted considerable interest as potential therapeutic targets to prevent or delay the onset of type 2 diabetes. While several factors promoting beta cell proliferation have been identified, in the context of nutrient excess the roles of glucose or NEFA in relation to insulin resistance remain unclear. Here we tested the hypothesis that glucose and NEFA synergistically and reversibly promote beta cell proliferation in the context of nutrient-induced insulin resistance...
January 11, 2017: Diabetologia
https://www.readbyqxmd.com/read/28072777/pancreatic-islets-find-a-new-transplant-home-in-the-omentum
#4
Charles Schmidt
No abstract text is available yet for this article.
January 10, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28072753/engraftment-site-and-effectiveness-of-the-pan-caspase-inhibitor-f573-to-improve-engraftment-in-mouse-and-human-islet-transplantation-in-mice
#5
Andrew R Pepper, Antonio Bruni, Rena Pawlick, John Wink, Yasmin Rafiei, Boris Gala-Lopez, Mariusz Bral, Nasser Abualhassan, Tatsuya Kin, A M James Shapiro
BACKGROUND: Islet transplantation is an effective therapy in type 1 diabetes and recalcitrant hypoglycemia. However, there is an ongoing need to circumvent islet loss posttransplant. We explore herein the potential of the pan-caspase inhibitor F573, to mitigate early apoptosis-mediated islet death within portal and extrahepatic portal sites in mice. METHODS: Mouse or human islets were cultured in standard media ±100 μM F573 and subsequently assessed for viability and apoptosis via TUNEL staining and caspase-3 activation...
January 9, 2017: Transplantation
https://www.readbyqxmd.com/read/28069642/alpha-1-antitrypsin-enhances-islet-engraftment-by-suppression-of-instant-blood-mediated-inflammatory-reaction
#6
Jingjing Wang, Zhen Sun, Wenyu Gou, David B Adams, Wanxing Cui, Katherine A Morgan, Charlie Strange, Hongjun Wang
Islet cell transplantation has limited effectiveness because of an instant blood-mediated inflammatory reaction (IBMIR) that occurs immediately after cell infusion and leads to dramatic β cell death. In intraportal islet transplantation models using mouse and human islets, we demonstrated that alpha-1 antitrypsin (AAT, Prolastin-C), a serine protease inhibitor used for the treatment of AAT deficiency, inhibits IBMIR and cytokine-induced inflammation in islets. In mice, more diabetic recipients reached normoglycemia after intraportal islet transplantation when they were treated with AAT compared to mice treated with saline...
January 9, 2017: Diabetes
https://www.readbyqxmd.com/read/28069641/differential-impact-of-chronic-hyperglycemia-on-humoral-versus-cellular-primary-alloimmunity
#7
Nicholas H Bishop, Michelle K Nelsen, K Scott Beard, Ronald G Gill
Diabetes is prevalent among solid organ transplant recipients and is universal among islet transplant recipients. While diabetes is often considered to result in an immune compromised state, the impact of chronic hyperglycemia on host alloimmunity is not clear. Potential immune modifying effects of obesity, autoimmunity, or diabetogenic agents like streptozotocin may confound understanding alloimmunity in experimental models of diabetes. Therefore, we sought to determine the role of chronic hyperglycemia due to insulinopenia on alloimmunity using the non-autoimmune, spontaneously diabetic H-2(b)-expressing C57BL/6 Ins2(Akita) mice (Akita)...
January 9, 2017: Diabetes
https://www.readbyqxmd.com/read/28066985/from-micro-to-macro-the-hierarchical-design-in-a-micropatterned-scaffold-for-cell-assembling-and-transplantation
#8
Kai Wang, Xi Wang, Chengsheng Han, Wenda Hou, Jinyang Wang, Liangyi Chen, Ying Luo
A microwell-patterned membranous scaffold that integrates nano- and microscale topographical characteristics based on polyurethane is fabricated for transplanting syngeneic islets and allogeneic mesenchymal stem cells into diabetic rodents. The scaffold effectively allows for assembling of single cells/microtissues, enables the transplantation of cells with spatial control, and improves the transplant's engraftment efficacy in vivo for treating diabetes.
January 2017: Advanced Materials
https://www.readbyqxmd.com/read/28058779/dual-role-of-il-1%C3%AE-in-islet-amyloid-formation-and-its-%C3%AE-cell-toxicity-implications-in-type-2-diabetes-and-islet-transplantation
#9
Yoo Jin Park, Garth L Warnock, Ziliang Ao, Nooshin Safikhan, Mark Meloche, Ali Asadi, Timothy J Kieffer, Lucy Marzban
AIMS/HYPOTHESIS: Islet amyloid, formed by aggregation of human islet amyloid polypeptide (hIAPP), contributes to β-cell failure in type 2 diabetes, cultured and transplanted islets. We previously showed that biosynthetic hIAPP aggregates induce β-cell Fas upregulation and activation of the Fas apoptotic pathway. Here, we used cultured human and hIAPP-expressing mouse islets to investigate: (1) the role of IL-1β in amyloid-induced Fas upregulation; (2) the effects of IL-1β-induced β-cell dysfunction on proIAPP processing and amyloid formation...
January 6, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28058735/safe-use-of-anti-cd154-monoclonal-antibody-in-pig-islet-xenotransplantation-in-monkeys
#10
Rita Bottino, Michael F Knoll, Joshua Graeme-Wilson, Edwin C Klein, David Ayares, Massimo Trucco, David K C Cooper
Anti-CD154mAb is a powerful co-stimulation blockade agent that is efficacious in preventing rejection, even in xenogeneic settings. It has been used in the majority of successful long-term pig-to-non-human primate islet transplantation models. However, its clinical use was halted as a result of thromboembolic complications that were also observed in preclinical and clinical organ transplantation models. An anti-CD154mAb was administered to 14 streptozotocin-induced diabetic cynomolgus monkey recipients of porcine islets, some of which received the agent for many months...
January 6, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28049286/is-islet-transplantation-a-realistic-approach-to-curing-diabetes
#11
REVIEW
Sang-Man Jin, Kwang-Won Kim
Since the report of type 1 diabetes reversal in seven consecutive patients by the Edmonton protocol in 2000, pancreatic islet transplantation has been reappraised based on accumulated clinical evidence. Although initially expected to therapeutically target long-term insulin independence, islet transplantation is now indicated for more specific clinical benefits. With the long-awaited report of the first phase 3 clinical trial in 2016, allogeneic islet transplantation is now transitioning from an experimental to a proven therapy for type 1 diabetes with problematic hypoglycemia...
January 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28017506/insulin-producing-cells-generation-by-overexpression-of-mir-375-in-adipose-derived-mesenchymal-stem-cells-from-diabetic-patients
#12
Mehran Piran, Seyed Ehsan Enderami, Mehrdad Piran, Hadis Soltani Sedeh, Ehsan Seyedjafari, Abdolreza Ardeshirylajimi
Diabetes Mellitus (DM) is a systematic disease, which happens because of destruction of islets of Langerhans in the pancreas and systematic resistance to insulin. The lack of donor for pancreas transplantation and risk of transplant rejection is the main challenge in the treatment of this disease. Stem cells are proper and sufficient source for creating insulin-producing cells (IPC). In this study adipose tissue was provided from diabetic patients operated for liposuction and then adipose derived stem cells (ADSCs) were isolated, characterized and then treated by lentiviruses containing miR-375, after 7, 14 and 21 days of induction, islet-like clusters (ILC) specific genes including insulin and PDX1 were evaluated by Real Time RT-PCR...
December 22, 2016: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28008169/advances-in-islet-encapsulation-technologies
#13
Tejal Desai, Lonnie D Shea
Type 1 diabetes is an autoimmune disorder in which the immune system attacks and destroys insulin-producing islet cells of the pancreas. Although islet transplantation has proved to be successful for some patients with type 1 diabetes, its widespread use is limited by islet donor shortage and the requirement for lifelong immunosuppression. An encapsulation strategy that can prevent the rejection of xenogeneic islets or of stem cell-derived allogeneic islets can potentially eliminate both of these barriers. Although encapsulation technology has met several challenges, the convergence of expertise in materials, nanotechnology, stem cell biology and immunology is allowing us to get closer to the goal of encapsulated islet cell therapy for humans...
December 23, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28006437/does-exercise-pose-a-challenge-to-glucoregulation-after-clinical-islet-transplantation
#14
Deanna R Funk, Normand G Boulé, Peter A Senior, Jane E Yardley
Islet transplantation (ITx) is effective in preventing severe hypoglycemia by restoring glucose-dependent insulin secretion in type 1 diabetes (T1D), but may not normalize glucose regulation. Studies suggest that physical activity plays a role in maintaining β-cell mass and function in individuals with type 2 diabetes and animal models of diabetes. This could indicate that physical activity plays a role in graft survival in ITx recipients. This review's objective is to assess current knowledge related to physical activity in ITx recipients...
January 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28003935/aggregation-of-engineered-human-%C3%AE-cells-into-pseudoislets-insulin-secretion-and-gene-expression-profile-in-normoxic-and-hypoxic-milieu
#15
Marie-José Lecomte, Séverine Pechberty, Cécile Machado, Sandra Da Barroca, Philippe Ravassard, Raphaël Scharfmann, Paul Czernichow, Bertrand Duvillié
Innovative treatments to cure type 1 diabetes are being actively researched. Among the different strategies, the replacement of β-cells has given promising results. Classically, islets from cadaveric donors are transplanted into diabetic patients, but recently phase I clinical trials that use stem cell-derived β-cells have been started. Such protocols require either an immunosuppressive treatment or the macroencapsulation of the β-cells. They involve cell aggregation and the exposure of the cells to hypoxia...
December 3, 2016: Cell Medicine
https://www.readbyqxmd.com/read/27999871/loss-of-prohormone-convertase-2-promotes-beta-cell-dysfunction-in-a-rodent-transplant-model-expressing-human-pro-islet-amyloid-polypeptide
#16
Jaques A Courtade, Evan Y Wang, Paul Yen, Derek L Dai, Galina Soukhatcheva, Paul C Orban, C Bruce Verchere
AIMS/HYPOTHESIS: A contributor to beta cell failure in type 2 diabetes and islet transplants is amyloid formation by aggregation of the beta cell peptide, islet amyloid polypeptide (IAPP). Similar to the proinsulin processing pathway that generates insulin, IAPP is derived from a prohormone precursor, proIAPP, which requires cleavage by prohormone convertase (PC) 1/3 and PC2 in rodent pancreatic beta cells. We hypothesised that loss of PC2 would promote beta cell death and dysfunction in a rodent model of human beta cell proIAPP overexpression...
December 20, 2016: Diabetologia
https://www.readbyqxmd.com/read/27990829/-islet-transplantation-as-a-treatment-for-hypoglycemia-unawareness-syndrome-evaluation-of-the-pilot-program-and-comparison-with-pancreas-transplantation
#17
Martina Zahradnická, Peter Girman, Jan Kříž, Zuzana Berková, Tomáš Koblas, Ema Vávrová, Lucie Kosinová, David Habart, Eva Fábryová, Eva Dovolilová, Tomáš Neškudla, Jan Peregrin, Jozef Kováč, Květoslav Lipár, Matěj Kočík, Lenka Németová, Jiří Svoboda, František Saudek
Islet transplantation (ITx) started in 2005 in IKEM as a potentially safer alternative to pancreas transplantation (PTx), which so far had represented the method of choice in type-1 diabetic patients with conservatively intractable hypoglycemia unawareness syndrome. The aim of the study was to compare these two methods with regard to severe hypoglycemia elimination and to frequency of complications.Up to November 2015 a total number of 48 patients underwent ITx. The results from 22 patients with hypoglycemia unawareness were statistically analyzed...
2016: Casopís Lékar̆ů C̆eských
https://www.readbyqxmd.com/read/27989895/intraperitoneal-injection-of-ido-expressing-dermal-fibroblasts-improves-the-allograft-survival
#18
Mohsen Khosravi-Maharlooei, MohammadReza Pakyari, Reza B Jalili, Ruhangiz T Kilani, Aziz Ghahary
Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme with tolerogenic effects on different immune cells. Our group has previously shown that co-transplantation of IDO-expressing fibroblasts with donor tissues can delay immune rejection by inducing local immunosuppression. In this study, we have employed a systemic approach to improve allograft survival without using any immunosuppressive medication. To achieve this, 10 million lentiviral transduced IDO-expressing donor derived fibroblasts were injected into the peritoneal cavity of allograft recipients...
October 29, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27987245/quantitative-and-longitudinal-imaging-of-intramuscular-transplanted-islets-of-langerhans-with-spect-using-123-i-ibzm
#19
Stefanie M A Willekens, Inge van der Kroon, Desirée Bos, Lieke Joosten, Cathelijne Frielink, Otto C Boerman, Maarten Brom, Martin Gotthardt
A non-invasive imaging method to monitor islet grafts could provide novel and improved insight in the fate of transplanted islets and potentially monitor the effect of therapeutic interventions. Therefore, such an imaging method could help improve long-term transplantation outcome. Here, we investigated the use of [(123) I]IBZM for insulin positive graft volume quantification and longitudinal graft monitoring. SPECT images were acquired six weeks after islet transplantation in the calf muscle of rats. For longitudinal graft analysis, rats were monitored by SPECT for ten weeks...
December 17, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27982034/a-tlr9-agonist-promotes-il-22-dependent-pancreatic-islet-allograft-survival-in-type-1-diabetic-mice
#20
Deepak Tripathi, Sambasivan Venkatasubramanian, Satyanarayana S Cheekatla, Padmaja Paidipally, Elwyn Welch, Amy R Tvinnereim, Ramakrishna Vankayalapati
Pancreatic islet transplantation is a promising potential cure for type 1 diabetes (T1D). Islet allografts can survive long term in the liver parenchyma. Here we show that liver NK1.1(+) cells induce allograft tolerance in a T1D mouse model. The tolerogenic effects of NK1.1(+) cells are mediated through IL-22 production, which enhances allograft survival and increases insulin secretion. Increased expression of NKG2A by liver NK1.1(+) cells in islet allograft-transplanted mice is involved in the production of IL-22 and in the reduced inflammatory response to allografts...
December 16, 2016: Nature Communications
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