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Islet cell transplantation

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https://www.readbyqxmd.com/read/28639386/development-of-immune-response-to-tissue-restricted-self-antigens-in-simultaneous-kidney-pancreas-transplant-recipients-with-acute-rejection
#1
Muthukumar Gunasekaran, Neeta Vachharajani, Joseph P Gaut, Thin Thin Maw, Rowena Delos Santos, Surendra Shenoy, William C Chapman, Jason Wellen, Thalachallour Mohanakumar
Simultaneous kidney-pancreas transplantation (SKP Tx) is a treatment for end-stage kidney disease secondary to diabetes mellitus. We investigated the role of immune responses to donor human leukocyte antigens (HLA) and tissue-restricted kidney and pancreas self-antigens (KSAgs and PSAgs, respectively) in SKP Tx recipients (SKP TxRs). Sera collected from 39 SKP TxRs were used to determine de novo Abs specific for KSAgs (collagen-IV, Col-IV; fibronectin, FN) and PSAgs (insulin, islet cells, glutamic acid decarboxylase, and pancreas-associated protein-1) by ELISA...
June 21, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28637827/islet-encapsulation-physiological-possibilities-and-limitations
#2
Olle Korsgren
A logical cure for type 1 diabetes (T1D) involves replacing the lost insulin-producing cells with new ones, preferably cells from a well-characterized and unlimited source of human insulin-producing cells. This straightforward and simple solution to provide a cure for T1D is immensely attractive but entails at least two inherent and thus far unresolved hurdles: 1) provision of an unlimited source of functional human insulin-producing cells and 2) prevention of rejection without the side effects of systemic immunosuppression...
July 2017: Diabetes
https://www.readbyqxmd.com/read/28632821/encapsulated-islet-transplantation-where-do-we-stand
#3
Vijayaganapathy Vaithilingam, Sumeet Bal, Bernard E Tuch
Transplantation of pancreatic islets encapsulated within immuno-protective microcapsules is a strategy that has the potential to overcome graft rejection without the need for toxic immunosuppressive medication. However, despite promising preclinical studies, clinical trials using encapsulated islets have lacked long-term efficacy, and although generally considered clinically safe, have not been encouraging overall. One of the major factors limiting the long-term function of encapsulated islets is the host's immunological reaction to the transplanted graft which is often manifested as pericapsular fibrotic overgrowth (PFO)...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28632820/the-nexus-of-stem-cell-derived-beta-cells-and-genome-engineering
#4
Sara D Sackett, Aida Rodriguez, Jon S Odorico
Diabetes, type 1 and type 2 (T1D and T2D), are diseases of epidemic proportions, which are complicated and defined by genetics, epigenetics, environment, and lifestyle choices. Current therapies consist of whole pancreas or islet transplantation. However, these approaches require life-time immunosuppression, and are compounded by the paucity of available donors. Pluripotent stem cells have advanced research in the fields of stem cell biology, drug development, disease modeling, and regenerative medicine, and importantly allows for the interrogation of therapeutic interventions...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28623861/level-of-acceptance-of-islet-cell-and-kidney-xenotransplants-by-personnel-of-hospitals-with-and-without-experience-in-clinical-xenotransplantation
#5
Adrian Abalovich, Shinichi Matsumoto, Carlos J Wechsler, Mariana E Carulla, Martín E Siciliano, Daniel Sznaider, Joachim Denner, Robert B Elliott
BACKGROUND: Recently, significant progress in both safety and efficacy has been achieved in the field of xenotransplantation, as exemplified by results from the first clinical trials of porcine islet transplantation. It would be of interest to learn whether the attitude of the clinical staff involved in such trials changes as the trials are carried out in their own hospital. METHODS: One hundred and four clinical staff members from the Eva Peron Hospital of San Martin (Buenos Aires, Argentina) where clinical trials of islet xenotransplantation have been performed and 92 similar staff members from the Diego Thompson Hospital (Buenos Aires, Argentina) where no such xenotransplantation has been carried out participated in the study...
June 17, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28620237/lea29y-expression-in-transgenic-neonatal-porcine-islet-like-cluster-promotes-long-lasting-xenograft-survival-in-humanized-mice-without-immunosuppressive-therapy
#6
L Wolf-van Buerck, M Schuster, F S Oduncu, A Baehr, T Mayr, S Guethoff, J Abicht, B Reichart, N Klymiuk, E Wolf, J Seissler
Genetically engineered pigs are a promising source for islet cell transplantation in type 1 diabetes, but the strong human anti-pig immune response prevents its successful clinical application. Here we studied the efficacy of neonatal porcine islet-like cell clusters (NPICCs) overexpressing LEA29Y, a high-affinity variant of the T cell co-stimulation inhibitor CTLA-4Ig, to engraft and restore normoglycemia after transplantation into streptozotocin-diabetic NOD-SCID IL2rγ(-/-) (NSG) mice stably reconstituted with a human immune system...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28616498/xenotransplantation-a-special-case-of-one-health
#7
REVIEW
Joachim Denner
The chronic shortage of human transplants to treat tissue and organ failure has led to the development of xenotransplantation, the transplantation of cells, tissues and organs from another species to human recipients. For a number of reasons, pigs are best suited as donor animals. Successful, routine xenotransplantation would have an enormous impact on the health of the human population, including the young, who sometimes require a replacement organ or islet cells, but especially the elderly, who more often suffer the consequences of organ failure...
June 2017: One Health
https://www.readbyqxmd.com/read/28611473/apc-targeted-proinsulin-expression-inactivates-insulin-specific-memory-cd8-t-cells-in-nod-mice
#8
Peta Ls Reeves, Rajeev Rudraraju, Xiao Liu, F Susan Wong, Emma E Hamilton-Williams, Raymond J Steptoe
Type 1 diabetes (T1D) results from T-cell mediated autoimmune destruction of pancreatic β cells. Effector T-cell responses emerge early in disease development and expand as disease progresses. Following β cell destruction, a long-lived T-cell memory is generated that represents a barrier to islet transplantation and other cellular insulin-replacement therapies. Development of effective immunotherapies that control or ablate β cell destructive effector and memory T cell responses has the potential to prevent disease progression and recurrence...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28600038/potential-differentiation-of-islet-like-cells-from-pregnant-cow-derived-placental-stem-cells
#9
Shao-Yu Peng, Chien-Wen Chou, Yu-Hsuan Kuo, Perng-Chih Shen, S W Steven Shaw
OBJECTIVE: Type 1 diabetes is an autoimmune disease that destroys islet cells and results in insufficient insulin secretion by pancreatic β-cells. Islet transplantation from donors is an approach used for treating patients with diabetes; however, this therapy is difficult to implement because of the lack of donors. Nevertheless, several stem cells have the potential to differentiate from islet-like cells and enable insulin secretion for treating diabetes in animal models. For example, placenta is considered a waste material and can be harvested noninvasively during delivery without ethical or moral concerns...
June 2017: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28596584/rcan-11r-peptide-provides-immunosuppression-for-fully-mismatched-islet-allografts-in-mice
#10
Hirofumi Noguchi, Koji Sugimoto, Chika Miyagi-Shiohira, Yoshiki Nakashima, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Yasufumi Noguchi
Calcineurin inhibitors have been used for transplant therapy. However, the inhibition of calcineurin outside the immune system has a number of side effects. We previously developed a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells) using the polyarginine peptide delivery system. This peptide (11R-VIVIT) selectively interferes with calcineurin-NFAT interaction without affecting the activity of calcineurin phosphatase and provides immunosuppression for fully mismatched islet allografts in mice...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28584077/vascular-sprouts-induce-local-attraction-of-proangiogenic-neutrophils
#11
Gustaf Christoffersson, Jalal Lomei, Paul O'Callaghan, Johan Kreuger, Stefan Engblom, Mia Phillipson
Angiogenesis, the growth of new blood vessels, is a complex process requiring the orchestration of numerous different cell types, growth factors, and chemokines. Some of the recently acknowledged actors in this process are immune cells. They accumulate at hypoxic sites, but the kinetics, dynamics, and regulation of that trafficking are unknown. In this study, we used intravital and live cell imaging to understand how neutrophils and macrophages migrate and behave at angiogenic sites. We developed two reproducible models of angiogenesis: one by transplanting isolated and hypoxic pancreatic islets into the cremaster muscles of mice, and another by in vitro coculturing of mouse aortic rings with neutrophils...
June 5, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28583545/simultaneous-subtotal-pancreatectomy-and-streptozotocin-injection-for-diabetes-modeling-in-cynomolgus-monkeys
#12
H Park, J B Park, J H Kim, K W Lee, H S Lee, G-S Kim, D-Y Shin, S-H Oh, S-M Jin, S J Kim
BACKGROUND: In an experimental animal model of islet transplantation, stable induction of insulin-dependent diabetes mellitus (IDDM) and islet isolation from donor pancreas are essential. Total pancreatectomy for IDDM induction and islet procurement in nonhuman primates leads to unwanted loss of exocrine function and may lead to morbidities associated with IDDM. METHODS: IDDM induction with streptozotocin (STZ) is associated with drug toxicity of STZ and necessitates the killing of another animal for islet procurement...
June 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28575981/pancreatic-islet-surface-bioengineering-with-a-heparin-incorporated-starpeg-nanofilm
#13
Shaofeng Lou, Xiuyuan Zhang, Jimin Zhang, Juan Deng, Deling Kong, Chen Li
Cell surface engineering could protect implanted cells from host immune rejections while modify the cellular landscape for better post-transplantation graft function and survival. Islet transplantation is considered the most promising therapeutic option with the potential to cure diabetes. Current approach to improve clinical efficacy of pancreatic islet transplantation is alginate encapsulation. However, disappointing outcomes have been reported in clinical trials due to larger islet size resulted by encapsulation and alginate-elicited host immune responses...
September 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28562418/autologous-islet-transplantation-challenges-and-lessons
#14
Ty B Dunn, Joshua J Wilhelm, Melena D Bellin, Timothy L Pruett
PURPOSE OF REVIEW: Human islet isolation and autotransplantation [autologous islet transplant (AUTX)] is performed to prevent or ameliorate brittle diabetes after total pancreatectomy performed for benign disease. The success or failure of the transplant can be associated with a profound impact on the individual's quality of life and even survival. AUTX offers unique insights into the effects of pancreas quality, islet number, isolation technique and alternate site engraftment on transplant efficacy...
May 29, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28558297/mri-sensitive-contrast-agent-with-anticoagulant-activity-for-surface-camouflage-of-transplanted-pancreatic-islets
#15
Yong Hwa Hwang, Min Jun Kim, Dong Yun Lee
Pancreatic islet implantation in the liver is a promising approach for diabetes therapy. However, 70% of the islet mass fails to be engrafted in the liver due to the instant blood-mediated inflammatory reactions (IBMIR) resulting from direct contact between islet cells and the bloodstream. To overcome this issue, direct monitoring is very important for establishing prognosis after islet cell therapy. Here we established a new type of MR contrast agent with anticoagulant activity via heparin-immobilized superparamagnetic iron oxide (HSPIO)...
May 23, 2017: Biomaterials
https://www.readbyqxmd.com/read/28554010/a-bilaminated-decellularized-scaffold-for-islet-transplantation-structure-properties-and-functions-in-diabetic-mice
#16
Xi Wang, Kai Wang, Wei Zhang, Ming Qiang, Ying Luo
Ectopic transplantation of islets provides a beta cell-replacement approach that may allow the recovery of physiological regulation of the blood sugar level in patients with Type I diabetes (T1D). In development of new extrahepatic islet transplantation protocols in support of the islet engraftment, it is pivotal to develop scaffold materials with multifaceted functions to provide beneficial microenvironment, mediate host response in favor of vascularization/islet integration and maintain long-term islet function at the transplantation site...
May 22, 2017: Biomaterials
https://www.readbyqxmd.com/read/28553360/in-vivo-immunogenic-response-to-allogeneic-mesenchymal-stem-cells-and-the-role-of-preactivated-mesenchymal-stem-cells-cotransplanted-with-allogeneic-islets
#17
Régis Linhares Oliveira, Pedro Cesar Chagastelles, Patrícia Sesterheim, Patricia Pranke
Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into cells from the mesenchymal lineage. The hypoimmunogenic characteristic of MSCs has encouraged studies using allogeneic MSCs for the treatment of autoimmune diseases and inflammatory conditions. Promising preclinical results and the safety of allogeneic MSC transplantation have created the possibility of "off-the-shelf" clinical application of allogeneic cells. This study has aimed to evaluate the survival of untreated and IFN-γ- and TNF-α-treated (preactivated) allogeneic MSCs transplanted under the kidney capsule of immunocompetent mice together with the role of preactivated MSCs after cotransplantation with allogeneic islets...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28550730/transplantation-of-aire-overexpressing-bone-marrow-derived-dendritic-cells-delays-the-onset-of-type-1-diabetes
#18
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
#19
Argia Acarregui, Jesús Ciriza, Laura Saenz Del Burgo, Haritz Gurruchaga Iribar, José Yeste, Xavi Illa, Gorka Orive, Rosa M Hernández, Rosa Villa, Jose Luis Pedraz
Type I diabetes mellitus is characterised 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...
June 6, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28534310/combination-immunotherapy-for-type-1-diabetes
#20
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
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