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Islet cell transplantation

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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/28508555/laminin-and-collagen-iv-inclusion-in-immunoisolating-microcapsules-reduces-cytokine-mediated-cell-death-in-human-pancreatic-islets
#8
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
#9
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
#10
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/28489277/pancreas-after-islet-pai-transplantation-in-non-uremic-type-1-diabetes-a-strategy-for-restoring-durable-insulin-independence
#11
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/28484241/glial-cell-line-derived-neurotrophic-factor-protects-human-islets-from-nutrient-deprivation-and-endoplasmic-reticulum-stress-induced-apoptosis
#12
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
#13
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
#14
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/28467694/durable-control-of-autoimmune-diabetes-in-mice-achieved-by-intraperitoneal-transplantation-of-neo-islets-three-dimensional-aggregates-of-allogeneic-islet-and-mesenchymal-stem-cells
#15
Christof Westenfelder, Anna Gooch, Zhuma Hu, Jon Ahlstrom, Ping Zhang
Novel interventions that reestablish endogenous insulin secretion and thereby halt progressive end-organ damage and prolong survival of patients with autoimmune Type 1 diabetes mellitus (T1DM) are urgently needed. While this is currently accomplished with allogeneic pancreas or islet transplants, their utility is significantly limited by both the scarcity of organ donors and life-long need for often-toxic antirejection drugs. Coadministering islets with bone marrow-derived mesenchymal stem cells (MSCs) that exert robust immune-modulating, anti-inflammatory, anti-apoptotic, and angiogenic actions, improves intrahepatic islet survival and function...
May 3, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28457422/co-transplantation-of-xenogeneic-bone-marrow-derived-mesenchymal-stem-cells-alleviates-rejection-of-pancreatic-islets-in-non-obese-diabetic-mice
#16
C Corradi-Perini, T M Santos, N O S Camara, M C Riella, C A M Aita
Bone marrow-mesenchymal stem cells (BM-MSCs) have generated a great perspective in the field of regenerative medicine, and also in the treatment of inflammatory and autoimmune diseases in the past decade due to their immunomodulatory and anti-inflammatory properties. Here, we investigated the effect of xenogeneic BM-MSCs and pancreatic islets co-transplantation obtained from Wistar rats in preventing rejection or inducing tolerance to islet transplantation in non-obese diabetic mice. Non-obese diabetic mice were treated with co-transplantation of pancreatic islets and BM-MSCs (islet + MSCs group) or pancreatic islets only (islet group)...
May 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28452488/metabolomics-study-of-the-effects-of-inflammation-hypoxia-and-high-glucose-on-isolated-human-pancreatic-islets
#17
Marta Garcia-Contreras, Alejandro Tamayo-Garcia, Kirk L Pappan, Gregory A Michelotti, Cherie L Stabler, Camillo Ricordi, Peter Buchwald
The transplantation of human pancreatic islets is a therapeutic possibility for a subset of type 1 diabetic patients who experience severe hypoglycemia. Pre- and post-transplantation loss in islet viability and function, however, is a major efficacy-limiting impediment. To investigate the effects of inflammation and hypoxia, the main obstacles hampering the survival and function of isolated, cultured, and transplanted islets, we conducted a comprehensive metabolomics evaluation of human islets in parallel with dynamic glucose-stimulated insulin release (GSIR) perifusion studies for functional evaluation...
May 9, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28451515/islet-cell-transplant-update-on-current-clinical-trials
#18
Christian Schuetz, James F Markmann
In the last 15 years clinical islet transplantation has made the leap from experimental procedure to standard of care for a highly selective group of patients. Due to a risk-benefit calculation involving the required systemic immunosuppression the procedure is only considered in patients with type 1 diabetes, complicated by severe hypoglycemia or end stage renal disease. In this review we summarize current outcomes of the procedure and take a look at ongoing and future improvements and refinements of beta cell therapy...
September 2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/28450972/circulating-unmethylated-insulin-dna-as-a-potential-non-invasive-biomarker-of-beta-cell-death-in-type-1-diabetes-a-review-and-future-prospect
#19
REVIEW
Kuo Zhang, Guigao Lin, Yanxi Han, Jiehong Xie, Jinming Li
BACKGROUND: The early detection of type 1 diabetes (T1D) largely depends on a reliable approach to monitor β cell loss. An effective way to evaluate the decline of β cell mass would allow early preventative intervention to preserve insulin secretion. MAIN BODY: Recent progress in the development of novel biomarkers, based on tissue-specific methylation patterns, has inspired relevant studies in T1D. In this review, we focus on the application of circulating β cell-derived unmethylated insulin (INS) DNA...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28450387/composite-biomarker-panel-for-prediction-of-severity-and-diagnosis-of-acute-gvhd-with-t-cell-depleted-allogeneic-stem-cell-transplants-single-centre-pilot-study
#20
San San Min, Varun Mehra, Jennifer Clay, Gemma F Cross, Abdel Douiri, Tracy Dew, Tanya N Basu, Victoria Potter, M Mansour Ceesay, Antonio Pagliuca, Roy A Sherwood, Royce P Vincent
AIMS: Acute graft-versus-host disease (aGVHD) is a leading cause of morbidity and mortality following allogeneic haematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the clinical utility of a composite biomarker panel to help identify individuals at risk of developing aGVHD, and to help predict and differentiate between severity of aGVHD following T-cell-depleted allogeneic HSCT. METHODS: We retrospectively analysed our cohort of biopsy confirmed patients with aGVHD, who underwent T-cell-depleted HSCT and matched them with negative controls without any evidence of aGVHD...
April 27, 2017: Journal of Clinical Pathology
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