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Islet transplant

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https://www.readbyqxmd.com/read/29057561/pre-clinical-results-in-pig-to-non-human-primate-islet-xenotransplantation-using-anti-cd40-antibody-2c10r4-based-immunosuppression
#1
Jun-Seop Shin, Jong-Min Kim, Byoung-Hoon Min, Il Hee Yoon, Hyun Je Kim, Jung-Sik Kim, Yong-Hee Kim, Seong-Jun Kang, Jiyeon Kim, Hee-Jung Kang, Dong-Gyun Lim, Eung-Soo Hwang, Jongwon Ha, Sang-Joon Kim, Wan Beom Park, Chung-Gyu Park
BACKGROUND: Islet transplantation is an effective therapy for selected patients with type 1 diabetes with labile glycemic control and hypoglycemic unawareness, but donor organs are limited. Islet xenotransplantation using porcine islets will potentially solve this problem. Although successful proof of concept studies using clinically inapplicable anti-CD154 monoclonal antibody (mAb) in pig-to-non-human primate (NHP) islet xenotransplantation has been demonstrated by several groups worldwide, potentially clinically applicable anti-CD40 (2C10R4) mAb-based studies have not been reported...
October 22, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29051963/applications-of-particulate-oxygen-generating-substances-pogs-in-the-bioartificial-pancreas
#2
John P McQuilling, Sivanandane Sittadjody, Samuel Pendergraft, Alan C Farney, Emmanuel C Opara
Type-1 Diabetes (T1D) is a devastating autoimmune disorder which results in the destruction of beta cells within the pancreas. A promising treatment strategy for T1D is the replacement of the lost beta cell mass through implantation of immune-isolated microencapsulated islets referred to as the bioartificial pancreas. The goal of this approach is to restore blood glucose regulation and prevent the long-term comorbidities of T1D without the need for immunosuppressants. A major requirement in the quest to achieve this goal is to address the oxygen needs of islet cells...
October 20, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/29048258/selection-of-implantation-sites-for-transplantation-of-encapsulated-pancreatic-islets
#3
Haitao Zhu, Wenjing Li, Zhongwei Liu, Wenliang Li, Niuniu Chen, Linlin Lu, Wei Zhang, Zhen Wang, Bo Wang, Kaili Pan, Xiaoge Zhang, Guoqiang Chen
Pancreatic islet transplantation has been validated as a valuable therapy for type 1 diabetes mellitus patients with exhausted insulin treatment. However, this therapy remains limited by the shortage of donor and the requirement of lifelong immunosuppression. Islet encapsulation, as an available bioartificial pancreas (BAP), represents a promising approach to enable protecting islet grafts without or with minimal immunosuppression and possibly expanding the donor pool. In order to develop a clinically implantable BAP, some key aspects need to be taken into accounts: encapsulation material, capsule design and implantation site...
October 19, 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/29046484/t-cells-expressing-chimeric-antigen-receptor-promote-immune-tolerance
#4
Antonio Pierini, Bettina P Iliopoulou, Heshan Peiris, Magdiel Pérez-Cruz, Jeanette Baker, Katie Hsu, Xueying Gu, Ping-Ping Zheng, Tom Erkers, Sai-Wen Tang, William Strober, Maite Alvarez, Aaron Ring, Andrea Velardi, Robert S Negrin, Seung K Kim, Everett H Meyer
Cellular therapies based on permanent genetic modification of conventional T cells have emerged as a promising strategy for cancer. However, it remains unknown if modification of T cell subsets, such as Tregs, could be useful in other settings, such as allograft transplantation. Here, we use a modular system based on a chimeric antigen receptor (CAR) that binds covalently modified mAbs to control Treg activation in vivo. Transient expression of this mAb-directed CAR (mAbCAR) in Tregs permitted Treg targeting to specific tissue sites and mitigated allograft responses, such as graft-versus-host disease...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/29045546/characterization-of-adipose-tissue-product-quality-using-measurements-of-oxygen-consumption-rate
#5
Thomas M Suszynski, David A Sieber, Kathryn Mueller, Allen L Van Beek, Bruce L Cunningham, Jeffrey M Kenkel
Background: Fat grafting is a common procedure in plastic surgery but associated with unpredictable graft retention. Adipose tissue (AT) "product" quality is affected by the methods used for harvest, processing and transfer, which vary widely amongst surgeons. Currently, there is no method available to accurately assess the quality of AT. Objectives: In this study, we present a novel method for the assessment of AT product quality through direct measurements of oxygen consumption rate (OCR)...
October 13, 2017: Aesthetic Surgery Journal
https://www.readbyqxmd.com/read/29029025/insulin-deficient-mouse-%C3%AE-cells-do-not-fully-mature-but-can-be-remedied-through-insulin-replacement-by-islet-transplantation
#6
Adam Ramzy, Majid Mojibian, Timothy J Kieffer
Insulin receptor insufficiency in β-cells leads to impaired insulin secretion and reduced β-cell hyperplasia in response to hyperglycemia. Selective insulin receptor deficiency in β-cells in later embryological development may lead to compensatory β-cell hyperplasia. Though these findings suggest insulin signaling on the β-cell is important for β-cell function, they are confounded by loss of signaling by the IGFs through the insulin receptor. To determine if insulin itself is necessary for β-cell development and maturation, we performed a characterization of pancreatic islets in mice with deletions of both non-allelic insulin genes (Ins1-/-Ins2-/-)...
September 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/29026874/australia-and-new-zealand-islets-and-pancreas-transplant-registry-annual-report-2017-pancreas-waiting-list-recipients-and-donors
#7
Angela C Webster, James Hedley, Abhijit Patekar, Paul Robertson, Patrick J Kelly
This is a registry report from the Australia and New Zealand Islet and Pancreas Transplant Registry. We report data for all solid organ pancreas transplant activity from inception in 1984 to end of 2016. Data analysis was performed using Stata Software version 14 (StataCorp, College Station, Tex). From 1984 to 2016 a total of 756 solid organ pancreas transplants have been performed in Australia and New Zealand, in 738 individuals. In 2016, 55 people received a pancreas transplant. These transplants were performed in Auckland (4), Monash (22), and Westmead (29)...
October 2017: Transplantation Direct
https://www.readbyqxmd.com/read/29019814/the-optimization-of-the-prevascularization-procedures-for-improving-subcutaneous-islet-engraftment
#8
Satomi Suzuki Uematsu, Akiko Inagaki, Yasuhiro Nakamura, Takehiro Imura, Yasuhiro Igarashi, Ibrahim Fathi, Shigehito Miyagi, Noriaki Ohuchi, Susumu Satomi, Masafumi Goto
BACKGROUND: Subcutaneous islet transplantation (SC Tx) is associated with minimal invasiveness, but poor vascularization. Thus, the optimization of the prevascularization procedures is crucial for improving the outcomes. Although the effectiveness of basic fibroblast growth factor (bFGF) was reported, the optimal procedures remain unclear. We sought to optimize the prevascularization procedures including the use of a novel scaffold, recombinant peptide (RCP). METHODS: Devices containing various amount of bFGF with/without heparin, or RCP were implanted into the subcutaneous space of diabetic C57BL/6 mice...
October 10, 2017: Transplantation
https://www.readbyqxmd.com/read/29018828/repurposing-lesogaberan-to-promote-human-islet-cell-survival-and-%C3%AE-cell-replication
#9
Jide Tian, Hoa Dang, Angela Hu, Willem Xu, Daniel L Kaufman
The activation of β-cell's A- and B-type gamma-aminobutyric acid receptors (GABAA-Rs and GABAB-Rs) can promote their survival and replication, and the activation of α-cell GABAA-Rs promotes their conversion into β-cells. However, GABA and the most clinically applicable GABA-R ligands may be suboptimal for the long-term treatment of diabetes due to their pharmacological properties or potential side-effects on the central nervous system (CNS). Lesogaberan (AZD3355) is a peripherally restricted high-affinity GABAB-R-specific agonist, originally developed for the treatment of gastroesophageal reflux disease (GERD) that appears to be safe for human use...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28993044/risk-factors-for-early-readmission-after-total-pancreatectomy-and-islet-auto-transplantation
#10
Rauf Shahbazov, Bashoo Naziruddin, Kunal Yadav, Giovanna Saracino, Gumpei Yoshimatsu, Mazhar A Kanak, Ernest Beecherl, Peter T Kim, Marlon F Levy
BACKGROUND: Little published data exist examining causes of hospital readmission following total pancreatectomy with islet autotransplantation (TPIAT). METHODS: A retrospective analysis was performed of a prospectively collected institutional TPIAT database. Primary outcome was unplanned readmission to the hospital within 30 days from discharge. Reasons and risk factors for readmission as well as islet function were evaluated and compared by univariate and multivariate analysis...
October 6, 2017: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/28984038/beta-cell-replacement-strategies-for-diabetes
#11
Timothy J Kieffer, Knut Woltjen, Kenji Osafune, Daisuke Yabe, Nobuya Inagaki
Diabetes is characterized by elevated levels of blood glucose as a result of insufficient production of insulin from loss or dysfunction of pancreatic islet beta cells. Here we review several approaches to replace beta cells that were recently discussed at a symposium held in Kyoto, Japan. Transplant of donor human islets can effectively treat diabetes and eliminate the need for insulin injections, supporting research aimed at identifying abundant supplies of cells. Studies demonstrating the feasibility of producing mouse islets in rats support the concept of generating pigs with human pancreas that can serve as donors of human islets, although scientific and ethical challenges remain...
October 6, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28975176/deformability-based-microfluidic-separation-of-pancreatic-islets-from-exocrine-acinar-tissue-for-transplant-applications
#12
Walter B Varhue, Linda Langman, Molly Kelly-Goss, Morgan Lataillade, Kenneth L Brayman, Shayn Peirce-Cottler, Nathan S Swami
The long-term management of type-1 diabetes (T1D) is currently achieved through lifelong exogenous insulin injections. Although there is no cure for T1D, transplantation of pancreatic islets of Langerhans has the potential to restore normal endocrine function versus the morbidity of hypoglycemic unawareness that is commonly associated with sudden death among fragile diabetics. However, since endocrine islet tissues form a small proportion of the pancreas, sufficient islet numbers can be reached only by combining islets from multiple organ donors and the transplant plug contains significantly high levels of exocrine acinar tissue, thereby exacerbating immune responses...
October 4, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28968432/gene-expression-signature-predicts-human-islet-integrity-and-transplant-functionality-in-diabetic-mice
#13
Sunil M Kurian, Kevin Ferreri, Chia-Hao Wang, Ivan Todorov, Ismail H Al-Abdullah, Jeffrey Rawson, Yoko Mullen, Daniel R Salomon, Fouad Kandeel
There is growing evidence that transplantation of cadaveric human islets is an effective therapy for type 1 diabetes. However, gauging the suitability of islet samples for clinical use remains a challenge. We hypothesized that islet quality is reflected in the expression of specific genes. Therefore, gene expression in 59 human islet preparations was analyzed and correlated with diabetes reversal after transplantation in diabetic mice. Analysis yielded 262 differentially expressed probesets, which together predict islet quality with 83% accuracy...
2017: PloS One
https://www.readbyqxmd.com/read/28964481/pediatric-pancreas-transplantation-including-total-pancreatectomy-with-islet-autotransplantation
#14
Alexander J Bondoc, Maisam Abu-El-Haija, Jaimie D Nathan
Unlike other solid-organ transplants, whole pancreas transplantation in children is relatively rare, and it occurs more frequently in the context of multivisceral or composite organ transplantation. Because children only infrequently suffer severe sequelae of type 1 diabetes mellitus, pancreas transplantation is rarely indicated in the pediatric population. More commonly, pediatric pancreas transplant occurs in the setting of incapacitating acute recurrent or chronic pancreatitis, specifically islet autotransplantation after total pancreatectomy...
August 2017: Seminars in Pediatric Surgery
https://www.readbyqxmd.com/read/28963731/ex-vivo-expanded-baboon-cd39%C3%A2-%C3%A2-regulatory-t-cells-prevent-rejection-of-porcine-islet-xenografts-in-nod-scid-il-2r%C3%AE-mice-reconstituted-with-baboon-peripheral-blood-mononuclear-cells
#15
Dandan Huang, Ya Wang, Wayne J Hawthorne, Min Hu, Joanne Hawkes, Heather Burns, Sussan Davies, Feng Gao, Yi Vee Chew, Shounan Yi, Philip J O'Connell
BACKGROUND: A high immunosuppressive burden is required for long-term islet xenograft survival in non-human primates even using genetically modified donor pigs. AIMS: We aimed to investigate the capacity of baboon regulatory T cells (Treg) to suppress islet xenograft rejection, thereby developing a potential immunoregulatory or tolerance therapy that could be evaluated in NHP models of xenotransplantation. MATERIALS & METHODS: Baboon Treg expanded with stimulation by porcine peripheral blood mononuclear cells (PBMC) were characterized by cell phenotyping and suppressive activity assays in vitro...
September 30, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28963457/kinetics-of-functional-beta-cell-mass-decay-in-a-diphtheria-toxin-receptor-mouse-model-of-diabetes
#16
Pim P van Krieken, Andrea Dicker, Maria Eriksson, Pedro L Herrera, Ulf Ahlgren, Per-Olof Berggren, Erwin Ilegems
Functional beta cell mass is an essential biomarker for the diagnosis and staging of diabetes. It has however proven technically challenging to study this parameter during diabetes progression. Here we have detailed the kinetics of the rapid decline in functional beta cell mass in the RIP-DTR mouse, a model of hyperglycemia resulting from diphtheria toxin induced beta cell ablation. A novel combination of imaging modalities was employed to study the pattern of beta cell destruction. Optical projection tomography of the pancreas and longitudinal in vivo confocal microscopy of islets transplanted into the anterior chamber of the eye allowed to investigate kinetics and tomographic location of beta cell mass decay in individual islets as well as at the entire islet population level...
September 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28962846/tunable-injectable-alginate-based-hydrogel-for-cell-therapy-in-type-1-diabetes-mellitus
#17
Albert Espona-Noguera, Jesús Ciriza, Alberto Cañibano-Hernández, Luis Fernandez, Ignacio Ochoa, Laura Saenz Del Burgo, Jose Luis Pedraz
Islet transplantation has the potential of reestablishing naturally-regulated insulin production in Type 1 diabetic patients. Nevertheless, this procedure is limited due to the low islet survival after transplantation and the lifelong immunosuppression to avoid rejection. Islet embedding within a biocompatible matrix provides mechanical protection and a physical barrier against the immune system thus, increasing islet survival. Alginate is the preferred biomaterial used for embedding insulin-producing cells because of its biocompatibility, low toxicity and ease of gelation...
September 27, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28962589/multipotent-mesenchymal-stromal-cells-enhance-insulin-secretion-from-human-islets-via-n-cadherin-interaction-and-prolong-function-of-transplanted-encapsulated-islets-in-mice
#18
Elisa Montanari, Raphael P H Meier, Redouan Mahou, Jörg D Seebach, Christine Wandrey, Sandrine Gerber-Lemaire, Leo H Buhler, Carmen Gonelle-Gispert
BACKGROUND: Multipotent mesenchymal stromal cells (MSC) enhance viability and function of islets of Langerhans. We aimed to examine the interactions between human MSC and human islets of Langerhans that influence the function of islets. METHODS: Human MSC and human islets (or pseudoislets, obtained after digestion and reaggregation of islet cells) were cocultured with or without cellular contact and glucose-stimulated insulin secretion assays were performed to assess cell function...
September 29, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28955189/the-diabetic-dog-as-a-translational-model-for-human-islet-transplantation%C3%A2
#19
REVIEW
Christopher A Adin, Chen Gilor
The dog model has served as the primary method for early development of many diabetes therapies, including pancreatic islet transplantation techniques and immunosuppressive protocols. Recent trends towards the use of monoclonal antibody therapies for immunosuppression in human islet transplantation have led to the increasing use of primate models with induced diabetes. In addition to induced-disease models in large animals, scientists in many fields are considering the use of naturally-occurring disease models in client-owned pets...
September 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28951824/intraocular-in%C3%A2-vivo-imaging-of-pancreatic-islet-cell-physiology-pathology
#20
REVIEW
Ingo B Leibiger, Per-Olof Berggren
BACKGROUND: Diabetes mellitus has reached epidemic proportions and requires new strategies for treatment. Unfortunately, the efficacy of treatment regimens on maintaining/re-gaining functional beta cell mass can, at the present, only be determined indirectly. Direct monitoring of beta cell mass is complicated by the anatomy of the endocrine pancreas, which consists of thousands to a million of discrete micro-organs, i.e. islets of Langerhans, which are scattered throughout the pancreas...
September 2017: Molecular Metabolism
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