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Islet transplant

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https://www.readbyqxmd.com/read/28550730/transplantation-of-aire-overexpressing-bone-marrow-derived-dendritic-cells-delays-the-onset-of-type-1-diabetes
#1
Dongbei Li, Bo Zhao, Yadong Luo, Steven Limbara, Bingjie Zhao, Xueyang Zou, Wei Yang, Yi Li
Autoimmune regulator (Aire) plays an indispensable role in maintaining central immune tolerance by promoting the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), which lead to the deletion of autoreactive T cells or the induction of Tregs and consequently prevent autoimmune disease development. Curing autoimmune diseases has always been a challenge. DC-based immunotherapy represents a new and effective method to establish tolerance...
May 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28535085/characterization-of-an-encapsulated-insulin-secreting-human-pancreatic-beta-cell-line-in-a-modular-microfluidic-device
#2
Argia Acarregui, Jesús Ciriza, Laura Saenz Del Burgo, Haritz Gurruchaga, José Yeste, Xavier Illa, Gorka Orive, Rosa M Hernández, Rosa Villa, Jose Luis Pedraz
Type I diabetes mellitus is characterized by the destruction of the insulin producing beta cells within the pancreas by the immune system. After the success of Edmonton protocol, islet transplantation has shown to be a promising therapy, but with the Achilles´ heel of the need of using immunosuppressive drugs. Currently, cell encapsulation technology represents a real alternative to protect transplanted islets from the host´s immune attack. Although preliminary in vitro studies with encapsulated cells have been traditionally performed under static conditions in terms of viability and efficiency, these static cultures do not represent a close approach to in vivo environments...
May 23, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28534310/combination-immunotherapy-for-type-1-diabetes
#3
REVIEW
Robert N Bone, Carmella Evans-Molina
PURPOSE OF REVIEW: Type 1 diabetes (T1D) is an autoimmune disease marked by β-cell destruction. Immunotherapies for T1D have been investigated since the 1980s and have focused on restoration of tolerance, T cell or B cell inhibition, regulatory T cell (Treg) induction, suppression of innate immunity and inflammation, immune system reset, and islet transplantation. The purpose of this review is to provide an overview and lessons learned from single immunotherapy trials, describe recent and ongoing combination immunotherapy trials, and provide perspectives on strategies for future combination clinical interventions aimed at preserving insulin secretion in T1D...
July 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28532691/bio-synthetic-materials-for-immunomodulation-of-islet-transplants
#4
Greg A Foster, Andrés J García
Clinical islet transplantation is an effective therapy in restoring physiological glycemic control in type 1 diabetics. However, allogeneic islets derived from cadaveric sources elicit immune responses that result in acute and chronic islet destruction. To prevent immune destruction of islets, transplant recipients require lifelong delivery of immunosuppressive drugs, which are associated with debilitating side effects. Biomaterial-based strategies to eliminate the need for immunosuppressive drugs are an emerging therapy for improving islet transplantation...
May 19, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28532102/islet-encapsulated-implantable-composite-hollow-fiber-membrane-based-device-a-bioartificial-pancreas
#5
Rohit S Teotia, Sachin Kadam, Atul Kumar Singh, Surendra Kumar Verma, Ashutosh Bahulekar, Sujata Kanetkar, Jayesh Bellare
Islets from xeno-sources and islet like clusters derived from autologus stem cells have emerged as alternatives to cadaveric pancreas used for treatment of type 1 diabetes. However, the immuno-isolation of these islets from the host immune system suffers from the issue of biocompatibility and hypoxia. To overcome the issues of immunobarrier biocompatibility, we developed a Polysulfone (Psf)/TPGS composite hollow fiber membrane (HFM) using a hollow fiber spinning pilot plant specially developed for this purpose...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28524456/endothelial-microparticles-released-by-activated-protein-c-protect-beta-cells-through-epcr-par1-and-annexin-a1-fpr2-pathways-in-islets
#6
Guillaume Kreutter, Mohamad Kassem, Ali El Habhab, Philippe Baltzinger, Malak Abbas, Julie Boisrame-Helms, Lamia Amoura, Jean Peluso, Blandine Yver, Zobairi Fatiha, Geneviève Ubeaud-Sequier, Laurence Kessler, Florence Toti
Islet transplantation is associated with early ischaemia/reperfusion, localized coagulation and redox-sensitive endothelial dysfunction. In animal models, islet cytoprotection by activated protein C (aPC) restores islet vascularization and protects graft function, suggesting that aPC triggers various lineages. aPC also prompts the release of endothelial MP that bear EPCR, its specific receptor. Microparticles (MP) are plasma membrane procoagulant vesicles, surrogate markers of stress and cellular effectors...
May 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28523592/islet-microencapsulation-strategies-and-clinical-status-in-diabetes
#7
REVIEW
Mustafa Omami, James J McGarrigle, Mick Reedy, Douglas Isa, Sofia Ghani, Enza Marchese, Matthew A Bochenek, Maha Longi, Yuan Xing, Ira Joshi, Yong Wang, José Oberholzer
PURPOSE OF REVIEW: Type 1 diabetes mellitus (T1DM) is an autoimmune disease that results from the destruction of insulin-producing pancreatic β cells in the islets of Langerhans. Islet cell transplantation has become a successful therapy for specific patients with T1DM with hypoglycemic unawareness. The reversal of T1DM by islet transplantation is now performed at many major medical facilities throughout the world. However, many challenges must still be overcome in order to achieve continuous, long-term successful transplant outcomes...
July 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28513004/effects-of-encapsulated-porcine-islets-on-glucose-and-c-peptide-concentrations-in-diabetic-nude-mice-6%C3%A2-months-after%C3%A2-intraperitoneal-transplantation
#8
Masuhiro Nishimura, Naho Iizuka, Yasutaka Fujita, Osamu Sawamoto, Shinichi Matsumoto
BACKGROUND: In patients with type 1 diabetes, allogeneic islet transplantation can provide normal HbA1c concentrations, but it requires immunosuppression. Transplanting encapsulated islets into the peritoneal cavity could reduce or eliminate the need for immunosuppression. One of the uncertain features of intraperitoneal islet transplantation is the difficulty of measuring C-peptide concentrations in peripheral blood, which is often used for the marker of islet function. We hypothesized that secreted C-peptide from intraperitoneally transplanted islets was mostly consumed in the peritoneal cavity, which resulted in low C-peptide concentrations in peripheral blood...
May 16, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28510280/modelling-the-iatrogenic-pancreatic-cancer-risk-after-islet-autotransplantation-in-mouse
#9
E Dugnani, V Pasquale, D Liberati, A Citro, E Cantarelli, S Pellegrini, P Marra, T Canu, G Balzano, M Scavini, A Esposito, C Doglioni, L Piemonti
Iatrogenic pancreatic cancer metastasis after islet infusion is a potential risk of islet autotransplantation performed after pancreatectomy. To model this risk islets and/or pancreatic exocrine clusters obtained from a genetically engineered mouse model for pancreatic ductal adenocarcinoma (the LSL-Kras(G12D/+) ;LSL-Trp53(R172H/+) ;Pdx-1-Cre, termed KPC mouse) were transplanted via the portal vein in syngeneic wild type (WT) severely diabetic recipients in the following treatment groups: group A (n=11) received KPC exocrine clusters in volume equal to 250 equivalent islets (IEQs); group B (n=12) received 250 WT IEQs mixed with KPC exocrine clusters (1:1 volume ratio); group C (n=5) received 250 KPC IEQs and group D (n=7) received 250 wild type IEQs...
May 16, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28508555/laminin-and-collagen-iv-inclusion-in-immunoisolating-microcapsules-reduces-cytokine-mediated-cell-death-in-human-pancreatic-islets
#10
Alberto Llacua, Bart J de Haan, Paul de Vos
Extracellular matrix (ECM) molecules have several functions in pancreatic islets including provision of mechanical support and prevention of cytotoxicity during inflammation. During islet isolation, ECM-connections are damaged and are not restored after encapsulation and transplantation. Inclusion of specific combinations of collagen type IV and laminins in immunoisolating capsules can enhance survival of pancreatic islets. Here we investigated whether ECM can also enhance survival and lower susceptibility of human islets to cytokine-mediated cytotoxicity...
May 16, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28507914/intra-islet-endothelial-cell-and-%C3%AE-cell-crosstalk-implication-for-islet-cell-transplantation
#11
REVIEW
Siddharth Narayanan, Gopalakrishnan Loganathan, Maheswaran Dhanasekaran, William Tucker, Ankit Patel, Venugopal Subhashree, SriPrakash Mokshagundam, Michael G Hughes, Stuart K Williams, Appakalai N Balamurugan
The intra-islet microvasculature is a critical interface between the blood and islet endocrine cells governing a number of cellular and pathophysiological processes associated with the pancreatic tissue. A growing body of evidence indicates a strong functional and physical interdependency of β-cells with endothelial cells (ECs), the building blocks of islet microvasculature. Intra-islet ECs, actively regulate vascular permeability and appear to play a role in fine-tuning blood glucose sensing and regulation...
April 24, 2017: World Journal of Transplantation
https://www.readbyqxmd.com/read/28506774/immunomodulatory-and-protective-effects-of-adipose-tissue-derived-mesenchymal-stem-cells-in-an-allograft-islet-composite-transplantation-for-experimental-autoimmune-type-1-diabetes
#12
Jamal Mohammadi Ayenehdeh, Bahare Niknam, Shim Rasouli, Seyed Mahmoud Hashemi, Hossein Rahavi, Nima Rezaei, Masoud Soleimani, Ali Liaeiha, Mohammad Hossein Niknam, Nader Tajik
BACKGROUND: Allogeneic islet transplantation could be an ideal alternative therapy for Type 1 Diabetes Mellitus (T1DM). Adipose Tissue-derived Mesenchymal Stem Cells (AT-MSCs) characterized by immunomodulatory and protective effects may have the potential to improve the outcome of this highly immunogenic transplant. METHODS: Syngenic AT-MSCs along with allograft islets embedded in hydrogelic composite and transplanted intraperitoneally in Streptozotocin (STZ) induced diabetic C57BL/6 mice...
May 12, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28492724/human-islet-xenotransplantation-in-rodents-a-literature-review-of-experimental-model-trends
#13
Leandro Ryuchi Iuamoto, André Silva Franco, Fábio Yuji Suguita, Felipe Futema Essu, Lucas Torres Oliveira, Juliana Mika Kato, Matheus Belloni Torsani, Alberto Meyer, Wellington Andraus, Eleazar Chaib, Luiz Augusto Carneiro D'Albuquerque
Among the innovations for the treatment of type 1 diabetes, islet transplantation is a less invasive method of treatment, although it is still in development. One of the greatest barriers to this technique is the low number of pancreas donors and the low number of pancreases that are available for transplantation. Rodent models have been chosen in most studies of islet rejection and type 1 diabetes prevention to evaluate the quality and function of isolated human islets and to identify alternative solutions to the problem of islet scarcity...
April 2017: Clinics
https://www.readbyqxmd.com/read/28489277/pancreas-after-islet-pai-transplantation-in-non-uremic-type-1-diabetes-a-strategy-for-restoring-durable-insulin-independence
#14
S A Wisel, J M Gardner, G R Roll, J Harbell, C E Freise, S Feng, S M Kang, R Hirose, D B Kaufman, A Posselt, P G Stock
Islet transplantation offers a minimally-invasive approach for beta cell replacement in diabetic patients with hypoglycemic unawareness. Attempts at insulin independence may require multiple islet re-infusions from distinct donors, thus increasing the risk for allogeneic sensitization. Currently, solid organ pancreas transplant is the only remaining surgical option following failed islet transplantation in the US. However, the immunologic impact of repeated exposure to donor antigens on subsequent pancreas transplantation is unclear...
May 10, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28486786/local-delivery-of-fingolimod-from-3-d-scaffolds-impacts-islet-graft-efficacy-and-microenvironment-in-a-murine-diabetic-model
#15
Anthony W Frei, Ying Li, Kaiyuan Jiang, Peter Buchwald, Cherie L Stabler
The local delivery of immunosuppressive agents could significantly promote the success of islet transplantation for the treatment of Type 1 diabetes. Fingolimod, a clinically-approved sphingosine-1-phosphate receptor agonist, has been found to dampen allograft islet rejection in rodent models when delivered systemically. Herein, we engineered a platform for the local delivery of fingolimod by incorporating it within a macroporous polydimethylsiloxane (PDMS) scaffold specifically designed for islet transplantation...
May 9, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28484241/glial-cell-line-derived-neurotrophic-factor-protects-human-islets-from-nutrient-deprivation-and-endoplasmic-reticulum-stress-induced-apoptosis
#16
Shadab Abadpour, Sven O Göpel, Simen W Schive, Olle Korsgren, Aksel Foss, Hanne Scholz
One of the key limitations to successful human islet transplantation is loss of islets due to stress responses pre- and post-transplantation. Nutrient deprivation and ER stress have been identified as important mechanisms leading to apoptosis. Glial Cell-line Derived Neurotrophic Factor (GDNF) has recently been found to promote islet survival after isolation. However, whether GDNF could rescue human islets from nutrient deprivation and ER stress-mediated apoptosis is unknown. Herein, by mimicking those conditions in vitro, we have shown that GDNF significantly improved glucose stimulated insulin secretion, reduced apoptosis and proinsulin:insulin ratio in nutrient deprived human islets...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28483491/long-term-cryopreservation-of-reaggregated-pancreatic-islets-resulting-in-successful-transplantation-in-rats
#17
Sonia Rawal, Stephen Harrington, S Janette Williams, Karthik Ramachandran, Lisa Stehno-Bittel
Preservation of pancreatic islets for long-term storage of islet used for transplantation or research has long been a goal. Unfortunately, few studies on long-term islet cryopreservation (1 month and longer) have reported positive outcomes in terms of islet yield, survival and function. In general, single cells have been shown to tolerate the cryopreservation procedure better than tissues/multicellular structures like islets. Thus, we optimized a method to cryopreserve single islet cells and, after thawing, reaggregated them into islet spheroids...
May 5, 2017: Cryobiology
https://www.readbyqxmd.com/read/28479244/role-of-pi3k-p110%C3%AE-in-the-differentiation-of-human-embryonic-stem-cells-into-islet-like-cells
#18
Gen-Hong Mao, Ping Lu, Ya-Nan Wang, Chen-Guang Tian, Xiao-Hui Huang, Zong-Gang Feng, Jin-Lan Zhang, Hong-Yang Chang
To investigate the effects of the PI3K inhibitors on the differentiation of insulin-producing cells derived from human embryonic stem cells. Here, we report that human embryonic stem cells induced by phosphatidylinositol-3-kinase (PI3K) p110β inhibitors could produce more mature islet-like cells. Findings were validated by immunofluorescence analysis, quantitative real-time PCR, insulin secretion in vitro and cell transplantation for the diabetic SCID mice. Immunofluorescence analysis revealed that unihormonal insulin-positive cells were predominant in cultures with rare polyhormonal cells...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28472471/successful-immunosuppressant-free-heterotopic-transplantation-of-tracheal-allografts-in-the-pig
#19
Julien De Wolf, Mathias Brieu, Christophe Zawadzki, Alexandre Ung, Eric Kipnis, Ramadan Jashari, Thomas Hubert, Pierre Fayoux, Christophe Mariette, Marie-Christine Copin, Alain Wurtz
OBJECTIVES: It has been demonstrated that both heterotopic and orthotopic transplants of epithelium-denuded cryopreserved tracheal allografts are feasible in immunosuppressant-free rabbits. Validation of these results in large animals is required before considering clinical applications. We evaluated the viability, immune tolerance and strain properties of such tracheal allografts heterotopically transplanted in a pig model. METHODS: Ten tracheal segments, 5 short (5 rings) and 5 long (10 rings), were obtained from male Landrace pigs...
May 2, 2017: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/28470672/stimulation-of-vascularization-of-a-subcutaneous-scaffold-applicable-for-pancreatic-islet-transplantation-enhances-immediate-post-transplant-islet-graft-function-but-not-long-term-normoglycemia
#20
Alexandra M Smink, Li Shiri, Daniël H Swart, Don T Hertsig, Bart J de Haan, Jan A A M Kamps, Leendert Schwab, Aart A van Apeldoorn, Eelco de Koning, Marijke M Faas, Jonathan R T Lakey, Paul de Vos
The liver as transplantation site for pancreatic islets is associated with significant loss of islets, which can be prevented by grafting in a prevascularized, subcutaneous scaffold. Supporting vascularization of a scaffold to limit the period of ischemia is challenging and was developed here by applying liposomes for controlled release of angiogenic factors. The angiogenic capacity of platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), acidic fibroblast growth factor (aFGF), and basic FGF (bFGF) were compared in a tube formation assay...
May 3, 2017: Journal of Biomedical Materials Research. Part A
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