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https://www.readbyqxmd.com/read/28444910/characterization-of-porcine-endogenous-retrovirus-expression-in-neonatal-and-adult-pig-pancreatic-islets
#1
Nizar I Mourad, Claire Crossan, Victoria Cruikshank, Linda Scobie, Pierre Gianello
BACKGROUND: Pig islets represent an alternative to the current modes of treatment for patients with diabetes. However, the concerns over pathogen transmission including that of PERV limit their immediate, widespread usage in humans. It has been previously demonstrated that PERV copy number and particularly expression levels can vary considerably between individuals and within different tissues of a single animal. In general, expression levels have been found to be particularly low in the pancreas compared to other porcine tissues suggesting a reduced risk associated with the use of this tissue...
April 26, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28433740/xenotransplantation-of-layer-by-layer-encapsulated-non-human-primate-islets-with-a-specified-immunosuppressive-drug-protocol
#2
Muhammad R Haque, Jiwoong Kim, Hyojun Park, Han Sin Lee, Kyo Won Lee, Taslim A Al-Hilal, Jee-Heon Jeong, Cheol-Hee Ahn, Doo Sung Lee, Sung Joo Kim, Youngro Byun
Islet transplantation is as effective as but also less immunogenic than pancreas transplantation for the treatment of type 1 diabetes mellitus. However, as the complete elimination of immunogenicity still remains a major obstacle in islet transplantation, layer-by-layer encapsulation (LbL) of pancreatic islets using biocompatible polymers offers a rational approach to reducing host immune response towards transplanted islets. We investigated the effect of LbL of non-human primate (NHP) islets on reducing immunogenicity as a preclinical model since NHPs have close phylogenetic and immunological relationship with human...
April 19, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28432571/cell-therapy-for-type-1-diabetes-current-and-future-strategies
#3
REVIEW
Yasaman Aghazadeh, Maria Cristina Nostro
PURPOSE OF THE REVIEW: Type 1 diabetes (T1D) is defined by an autoimmune destruction of insulin producing β-cells located in the endocrine part of the pancreas, the islets of Langerhans. As exogenous insulin administration fails at preventing severe complications associated with this disease, cell replacement therapies are being considered as a means to treat T1D. The purpose of this manuscript is to review the challenges associated with current strategies and discuss the potential of stem cell therapy for the treatment of T1D...
June 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28397308/improvement-of-isolated-caprine-islet-survival-and-functionality-in-vitro-by-enhancing-of-pdx1-gene-expression
#4
Homayoun Hani, Zeenathul Nazariah Allaudin, Mohd-Azmi Mohd-Lila, Kazhal Sarsaifi, Mina Rasouli, Yew Joon Tam, Tengku-Azmi Tengku-Ibrahim, Abas Mazni Othman
BACKGROUND: Dead islets replaced with viable islets are a promising offer to restore normal insulin production to a person with diabetes. The main reason for establishing a new islet source for transplantation is the insufficiency of human donor pancreas while using xenogeneic islets perhaps assists this problem. The expression of PDX1 is essential for the pancreas expansion. In mature β-cells, PDX1 has several critical roles such as glucose sensing, insulin synthesis, and insulin secretion...
April 11, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28385600/mesenchymal-stem-cells-and-differentiated-insulin-producing-cells-are-new-horizons-for-pancreatic-regeneration-in-type-i-diabetes-mellitus
#5
Ayat M Domouky, Ashraf S Hegab, Amal Al-Shahat, Nermin Raafat
BACKGROUND: Diabetes mellitus has become the third human killer following cancer and cardiovascular disease. Millions of patients, often children, suffer from type 1 diabetes (T1D). Stem cells created hopes to regenerate damaged body tissues and restore their function. AIM: This work aimed at clarifying and comparing the therapeutic potential of differentiated and non-differentiated mesenchymal stem cells (MSCs) as a new line of therapy for T1D. METHODS: 40 Female albino rats divided into group I (control): 10 rats and group II (diabetic), III and IV, 10 rats in each, were injected with streptozotocin (50mg/kg body weight)...
April 3, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28385584/a-study-of-the-clinical-utility-of-a-20-minute-secretin-stimulated-endoscopic-pancreas-function-test-and-performance-according-to-clinical-variables
#6
Luis F Lara, Morihito Takita, James S Burdick, Daniel C DeMarco, Ronnie R Pimentel, Tolga Erim, Marlon F Levy
BACKGROUND & AIMS: Direct pancreas juice testing of bicarbonate, lipase, or trypsin after stimulation by secretin or cholecystokinin (CCK) is used to determine exocrine function, a surrogate for diagnosing chronic pancreatitis (CP). Endoscopic pancreas function tests (ePFT) where a peak bicarbonate concentration (PBC) ≥80 mEq/L in pancreas juice is considered normal are now used more frequently. In this ePFT aspirates start 35 minutes after secretin administration because pancreas output peaks 30 minutes after secretagogue administration...
April 3, 2017: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/28360408/senescence-of-pancreas-in-middle-aged-rats-with-normal-vascular-function
#7
Mohamad Kassem, Zahid Rasul Niazi, Malak Abbas, Ali El Habhab, Guillaume Kreutter, Sonia Khemais-Benkhiat, Cyril Auger, Maria-Cristina Antal, Valérie B Schini-Kerth, Florence Toti, Laurence Kessler
BACKGROUND In organ transplantation, particularly pancreas transplantation, donor age is a determinant factor for graft survival. Physiological aging is crucial in the progressive deterioration of organs in adulthood. We compared the senescence and function features of pancreas and vascular tissues in young rats and middle-aged rats. MATERIAL AND METHODS Islet morphology and the area of cells secreting insulin or glucagon was investigated using immunohistology in young rats (12 weeks) and middle-aged rats (52 weeks) (n=8)...
March 31, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28360105/demethylation-of-induced-pluripotent-stem-cells-from-type-1-diabetic-patients-enhances-differentiation-into-functional-pancreatic-%C3%AE-cells
#8
Gohar S Manzar, Eun-Mi Kim, Nicholas Zavazava
Type 1 diabetes (T1D) can be managed by transplanting either the whole pancreas or isolated pancreatic islets. However, cadaveric pancreas is scarcely available for clinical use, limiting this approach. As such, there is a great need to identify alternative sources of clinically usable pancreatic tissues. Here, we used induced pluripotent stem (iPS) cells derived from patients with T1D to generate glucose-responsive, insulin-producing cells (IPCs) via 3D culture. Initially, T1D iPS cells were resistant to differentiation, but transient demethylation treatment significantly enhanced IPC yield...
March 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28340694/composition-and-organization-of-the-pancreatic-extracellular-matrix-by-combined-methods-of-immunohistochemistry-proteomics-and-scanning-electron-microscopy
#9
S Vigier, H Gagnon, K Bourgade, K Klarskov, T Fülöp, P Vermette
The epidemic expansion of diabetes is a major concern of public health. A promising treatment is the transplantation of islets of Langerhans isolated from the whole pancreas but the yields of islets isolation and the rates of successful engraftments still have to be improved to make this therapy effective. The extracellular matrix (ECM) of the pancreatic tissue is partially lost during the isolation process and a comprehensive knowledge of the pancreatic ECM composition and organization could identify targets to improve islets isolation and transplantation or highlight new therapeutics for pancreatic diseases...
January 2017: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/28324008/vessel-network-architecture-of-adult-human-islets-promotes-distinct-cell-cell-interactions-in-situ-and-is-altered-after-transplantation
#10
Christian M Cohrs, Chunguang Chen, Stephan R Jahn, Julia Stertmann, Helena Chmelova, Jürgen Weitz, Andrea Bähr, Nikolai Klymiuk, Anja Steffen, Barbara Ludwig, Virginia Kamvissi, Eckhard Wolf, Stefan R Bornstein, Michele Solimena, Stephan Speier
Islet cell hormone release is modulated by signals from endothelial and endocrine cells within the islet. However, models of intra-islet vascularization and paracrine cell signaling are mostly based on rodent pancreas. We here assessed for the first time the architecture and endocrine cell interaction of the vascular network in unperturbed human islets in situ and their potential to re-establish their endogenous vascular network after transplantation in vivo. We prepared pancreas tissue slices of fresh tissue obtained from non-diabetic patients undergoing partial pancreatectomy...
January 27, 2017: Endocrinology
https://www.readbyqxmd.com/read/28319566/pancreas-transplantation-from-pediatric-donors-a-unos-registry-analysis
#11
Mario Spaggiari, Martha Bissing, Maya Campara, Chun-Chieh Yeh, Ivo Tzvetanov, Hoonbae Jeon, Enrico Benedetti
BACKGROUND: Pancreas grafts from pediatric donors are still considered "not ideal". Perceived concerns are related to low islet mass and potential for graft thrombosis. METHODS: The study evaluated all pancreas transplants from January 2000 to May 2015 using the Organ Procurement and Transplant Network (OPTN) database. Comparative analysis of recipient and graft survival was performed between pediatric (≤18 years) and adult donors. In the pediatric group, the outcomes were stratified based on donor age (≤ 6 years; 7-12 years; 13-18 years) and weight (<30 kg; 30-95 Kg; >95 kg)...
March 18, 2017: Transplantation
https://www.readbyqxmd.com/read/28280376/single-donor-islet-transplantation-in-type-1-diabetes-patient-selection-and-special-considerations
#12
REVIEW
Jacob A Tatum, Max O Meneveau, Kenneth L Brayman
Type 1 diabetes mellitus is an autoimmune disorder of the endocrine pancreas that currently affects millions of people in the United States. Although the disease can be managed with exogenous insulin administration, the ultimate cure for the condition lies in restoring a patient's ability to produce their own insulin. Islet cell allotransplantation provides a means of endogenous insulin production. Though far from perfected, islet transplants are now a proven treatment for type 1 diabetics. However, proper patient selection is critical for achieving optimal outcomes...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28279194/crispr-targeted-genome-editing-of-mesenchymal-stem-cell-derived-therapies-for-type-1-diabetes-a-path-to-clinical-success
#13
REVIEW
Dario Gerace, Rosetta Martiniello-Wilks, Najah Therese Nassif, Sara Lal, Raymond Steptoe, Ann Margaret Simpson
Due to their ease of isolation, differentiation capabilities, and immunomodulatory properties, the therapeutic potential of mesenchymal stem cells (MSCs) has been assessed in numerous pre-clinical and clinical settings. Currently, whole pancreas or islet transplantation is the only cure for people with type 1 diabetes (T1D) and, due to the autoimmune nature of the disease, MSCs have been utilised either natively or transdifferentiated into insulin-producing cells (IPCs) as an alternative treatment. However, the initial success in pre-clinical animal models has not translated into successful clinical outcomes...
March 9, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28266040/ex-vivo-porcine-organ-perfusion-models-as-a-suitable-platform-for-translational-transplant-research
#14
Rohan Kumar, Wen Yuan Chung, Ashley Robert Dennison, Giuseppe Garcea
In transplantation surgery, extending the criteria for organ donation to include organs that may have otherwise been previously discarded has provided the impetus to improve organ preservation. The traditional method of cold static storage (CS) has been tried and tested and is suitable for organs meeting standard criteria donation. Ex vivo machine perfusion is, however, associated with evidence suggesting that it may be better than CS alone and may allow for organ donation criteria to be extended. Much of our knowledge of organ preservation is derived from animal studies...
March 6, 2017: Artificial Organs
https://www.readbyqxmd.com/read/28252345/evidence-of-stress-in-%C3%AE-cells-obtained-with-laser-capture-microdissection-from-pancreases-of-brain-dead-donors
#15
Aref Ebrahimi, Min-Ho Jung, Jonathan M Dreyfuss, Hui Pan, Dennis Sgroi, Susan Bonner-Weir, Gordon C Weir
Isolated islets used for transplantation are known to be stressed, which can result from the circumstances of death, in particular brain death, the preservation of the pancreas with its warm and cold ischemia, from the trauma of the isolation process, and the complex events that occur during tissue culture. The current study focused upon the events that occur before the islet isolation procedure. Pancreases were obtained from brain dead donors (n = 7) with mean age 50 (11) and normal pancreatic tissue obtained at surgery done for pancreatic neoplasms (n = 7), mean age 69 (9)...
March 4, 2017: Islets
https://www.readbyqxmd.com/read/28230643/mtor-inhibition-clinical-transplantation-pancreas-islet
#16
Thierry Berney, Axel Andres, Christian Toso, Pietro Majno, Jean-Paul Squifflet
This brief overview discusses the beneficial and deleterious effects of mTOR inhibitors on beta-cells, and how sirolimus- and everolimus-based immunosuppression have impacted on practices and outcomes of pancreas and islet transplantation. Sirolimus was the cornerstone of immunosuppressive regimens in islet transplantation at the turn of the millenium, but utilization of mTOR inhibitors has progressively decreased from >80% to <50% of islet transplant recipients in more recent years. For whole pancreas transplantation, mTOR inhibitors were used in approximately 20% of patients in the early 2000s, but this dropped over the years to <10% currently...
February 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28222054/ucp2-expression-is-increased-in-pancreas-from-brain-dead-donors-and-involved-in-cytokine-induced-%C3%AE-cells-apoptosis
#17
Leticia A Brondani, Tatiana H Rech, Gabriela Boelter, Andrea C Bauer, Cristiane B Leitão, Décio L Eizirik, Daisy Crispim
BACKGROUND: Systemic inflammation associated with brain death (BD) decreases islet yield and quality, negatively affecting outcomes of human islet transplantation. A recent study from our group showed an increased expression of uncoupling protein-2 (UCP2) in pancreas from rats with BD as compared with controls. UCP2 is located in the mitochondrial inner membrane and regulates production of reactive oxygen species and glucose-stimulated insulin secretion. It has been suggested that UCP2 also plays a role in β cell apoptosis, but these findings remain controversial...
March 2017: Transplantation
https://www.readbyqxmd.com/read/28201960/hypoglycemia-and-glucocorticoid-free-immunosuppression-are-related-with-low-dehydroepiandrosterone-sulfate-level
#18
Martina Zahradnicka, Frantisek Saudek, Kvetoslav Lipar, Jelena Skibova
BACKGROUND: Low dehydroepiandrosterone sulfate (DHEAS) levels and a high cortisol/DHEAS ratio are associated with higher mortality in elderly, dialyzed, and immunocompromised patients. The role of these hormones in patients with hypoglycemia unawareness (hypo) or in pancreas or islet recipients treated by glucocorticoid-free immunosuppressive regimen (IS) has not been studied. OBJECTIVE: The aim of this study was to determine the effects of IS and of recurrent hypoglycemia on DHEAS and adrenocorticotropic hormone (ACTH) levels in patients with type-1 diabetes (T1DM)...
February 13, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28188872/pre-transplantation-31-p-magnetic-resonance-spectroscopy-for-quality-assessment-of-human-pancreatic-grafts-a-feasibility-study
#19
Lina Carlbom, Jan Weis, Lars Johansson, Olle Korsgren, Håkan Ahlström
OBJECTIVE: To investigate the feasibility of using (31)P-MRS for objective non-invasive quality assessment of human pancreas grafts prior to transplantation or islet isolation. MATERIALS AND METHODS: Pancreata from 5 human donors, 3 males and 2 females, aged 49-78years, with body mass index (BMI) 22-31kg/m(2), were included. Pancreata were perfused with histidine-tryptophan-ketoglutarate solution during procurement and stored in hypothermic condition (4°C) for 21-44h...
February 8, 2017: Magnetic Resonance Imaging
https://www.readbyqxmd.com/read/28174674/the-evaluation-of-islet-purification-methods-that-use-large-bottles-to-create-a-continuous-density-gradient
#20
Chika Miyagi-Shiohira, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Yasufumi Noguchi, Masayuki Matsushita, Hirofumi Noguchi
Islet purification is one of the most important steps of islet isolation for pancreatic islet transplantation. The most common method of islet purification is density gradient centrifugation using a COBE 2991 cell processor. However, this method can damage islets mechanically through its high shearing force. We recently reported that a new purification method using large plastic bottles effectively achieves a high yield of islets from the porcine pancreas. In the present study, we evaluated the methods of making a continuous density gradient...
January 8, 2017: Cell Medicine
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