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pancreatic Transplant

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https://www.readbyqxmd.com/read/29338566/constructing-heparin-modified-pancreatic-decellularized-scaffold-to-improve-its-re-endothelialization
#1
Liancheng Xu, Yibing Guo, Yan Huang, Yicheng Xiong, Yang Xu, Xiaohong Li, Jingjing Lu, Lei Wang, Yao Wang, Yuhua Lu, Zhiwei Wang
Pancreas transplantation is considered as a promising therapeutic option with the potential to cure diabetes. However, efficacy of current clinical transplantation is limited by the donor organ. With regard to creating a functional pancreas-tissue equivalent for transplantation, vascularization remains a large obstacle. To enhance the angiogenic properties of pancreatic decellularized scaffold, surface modification of the vasculature was used to promote endothelialization efficiency. In this study, an endothelialized pancreatic decellularized scaffold was obtained through heparin modification under mild conditions...
January 1, 2018: Journal of Biomaterials Applications
https://www.readbyqxmd.com/read/29338388/novel-fusion-protein-targeting-mitochondrial-dna-improves-pancreatic-islet-functional-potency-and-islet-transplantation-outcomes
#2
Juan S Danobeitia, Peter J Chlebeck, Inna Shokolenko, Xiaobo Ma, Glenn Wilson, Luis A Fernandez
Long-term graft survival is an ongoing challenge in the field of islet transplantation. With the growing demand for transplantable organs, therapies to improve organ quality and reduce the incidence of graft dysfunction are of paramount importance. We evaluated the protective role of a recombinant DNA repair protein targeted to mitochondria (Exscien I-III), as a therapeutic agent using a rodent model of pancreatic islet transplantation. We first investigated the effect of therapy on isolated rat islets cultured with pro-inflammatory cytokines (interleukin-1 β, interferon γ, and tumor necrosis factor α) for 48 h and documented a significant reduction in apoptosis by flow cytometry, improved viability by immunofluorescence, and conserved functional potency in vitro and in vivo in Exscien I-III-treated islets...
November 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29337308/rage-binds-preamyloid-iapp-intermediates-and-mediates-pancreatic-%C3%AE-cell-proteotoxicity
#3
Andisheh Abedini, Ping Cao, Annette Plesner, Jinghua Zhang, Meilun He, Julia Derk, Sachi A Patil, Rosa Rosario, Jacqueline Lonier, Fei Song, Hyunwook Koh, Huilin Li, Daniel P Raleigh, Ann Marie Schmidt
Islet amyloidosis is characterized by the aberrant accumulation of islet amyloid polypeptide (IAPP) in pancreatic islets, resulting in β cell toxicity, which exacerbates type 2 diabetes and islet transplant failure. It is not fully clear how IAPP induces cellular stress or how IAPP-induced toxicity can be prevented or treated. We recently defined the properties of toxic IAPP species. Here, we have identified a receptor-mediated mechanism of islet amyloidosis-induced proteotoxicity. In human diabetic pancreas and in cellular and mouse models of islet amyloidosis, increased expression of the receptor for advanced glycation endproducts (RAGE) correlated with human IAPP-induced (h-IAPP-induced) β cell and islet inflammation, toxicity, and apoptosis...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29330294/establishment-of-the-first-well-differentiated-human-pancreatic-neuroendocrine-tumor-model
#4
Daniel Benten, Yasmin Behrang, Ludmilla Unrau, Victoria Weissmann, Gerrit Wolters-Eisfeld, Susanne Burdak-Rothkamm, Felix R Stahl, Martin Anlauf, Patricia Grabowski, Markus Möbs, Jan Dieckhoff, Bence Sipos, Martina Fahl, Corinna Eggers, Daniel Perez, Maximilian Bockhorn, Jakob R Izbicki, Ansgar W Lohse, Joerg Schrader
Clinical options for systemic therapy of neuroendocrine tumors (NET) are limited. Development of new drugs requires suitable representative in vitro and in vivo model systems. So far, the unavailability of a human model with a well-differentiated phenotype and typical growth characteristics has impaired pre-clinical research in NET. Herein, we establish and characterize a lymph node-derived cell line (NT-3) from a male patient with well-differentiated pancreatic NET. Neuroendocrine differentiation and tumor biology was compared to existing NET cell lines BON and QGP-1...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29325720/development-of-pancreatic-machine-perfusion-translational-steps-from-porcine-to-human-models
#5
Karim Hamaoui, Sally Gowers, Bynvant Sandhu, Natalie Vallant, Terry Cook, Martyn Boutelle, Daniel Casanova, Vassilios Papalois
BACKGROUND: Hypothermic machine perfusion (HMP) is increasingly being used for extended criteria kidney grafts. Pancreatic HMP is challenging because physiologically the pancreas is a low-flow organ susceptible to edema. We report the successful development of preclinical HMP models using porcine pancreases, as well as human pancreases unsuitable for clinical transplantation. METHODS: Ten porcine pancreases were used in the development of these perfusion models...
January 8, 2018: Journal of Surgical Research
https://www.readbyqxmd.com/read/29322561/effect-of-an-oxygen-generating-scaffold-on-the-viability-and-insulin-secretion-function-of-porcine-neonatal-pancreatic-cell-clusters
#6
Eun Mi Lee, Ji-In Jung, Zahid Alam, Hee-Gyeong Yi, Heejin Kim, Jin Woo Choi, Sunghoon Hurh, Young June Kim, Jong Cheol Jeong, Jaeseok Yang, Kook-Hwan Oh, Hee Chan Kim, Byeong Chun Lee, Inho Choi, Dong-Woo Cho, Curie Ahn
BACKGROUND: Islet encapsulation techniques have shown limited success in maintaining islet survival and function because encapsulation decreases oxygen supply. In this study, an oxygen-generating scaffold was fabricated to prevent hypoxic cell damage and improve the viability and insulin secretion of islets. METHODS: We fabricated an oxygen-generating scaffold by mixing calcium peroxide (CaO2 ) with polydimethylsiloxane (PDMS). We evaluated the effects of the oxygen-generating PDMS + CaO2 scaffold on viability, caspase-3 and caspase-7 activity, oxygen consumption rate (OCR), glucose-stimulated insulin secretion (GSIS), hypoxic cell marker expression, and reactive oxygen species (ROS) levels in porcine neonatal pancreatic cell clusters (NPCCs)...
January 10, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29321630/engineered-mesenchymal-stem-cell-sheets-patches-prevents-postoperative-pancreatic-leakage-in-a-rat-model
#7
Seong-Ryong Kim, Hye-Jin Yi, Yu Na Lee, Ji Yoon Park, Robert M Hoffman, Teruo Okano, In Kyong Shim, Song Cheol Kim
Post-operative pancreatic fistula (POPF) following pancreatic resection is a life-threatening surgical complication. Cell sheets were prepared and harvested using temperature-responsive culture dishes and transplanted as patches to seal POPF. Two different mesenchymal stem cell (MSC) sheets were compared in terms of the preventative ability for pancreatic leakage in a rat model. Both rat adipose-derived stem cell (rADSC) and bone marrow-derived stem cell (rBMSC) sheets were transplanted. Those rADSC and rBMSC sheets are created without enzymes and thus maintained their cell-cell junctions and adhesion proteins with intact fibronectin on the basal side, as well as characteristics of MSCs...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321484/loss-of-tolerance-to-gut-immunity-protein-glycoprotein-2-gp2-is-associated-with-progressive-disease-course-in-primary-sclerosing-cholangitis
#8
Tamas Tornai, David Tornai, Nora Sipeki, Istvan Tornai, Rayan Alsulaimani, Kai Fechner, Dirk Roggenbuck, Gary L Norman, Gabor Veres, Gabriella Par, Alajos Par, Ferenc Szalay, Peter Laszlo Lakatos, Peter Antal-Szalmas, Maria Papp
Glycoprotein 2[GP2] is a specific target of pancreatic autoantibodies[PAbs] in Crohn's disease(CD) and is involved in gut innate immunity processes. Our aim was to evaluate the prevalence and prognostic potential of PAbs in primary sclerosing cholangitis(PSC). Sixty-five PSC patients were tested for PAbs by indirect immunofluorescence and compared with healthy (n = 100) and chronic liver disease controls(CLD, n = 488). Additionally, a panel of anti-microbial antibodies and secretory (s)IgA levels were measured, as markers of bacterial translocation and immune dysregulation...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29320716/distinct-roles-of-systemic-and-local-actions-of-insulin-on-pancreatic-%C3%AE-cells
#9
Takumi Kitamoto, Kenichi Sakurai, Eun Young Lee, Koutaro Yokote, Domenico Accili, Takashi Miki
OBJECTIVE: Pancreatic β-cell mass and function are critical in glucose homeostasis. Their regulatory mechanisms have been studied principally under experimental conditions of reduced β-cell numbers, such as β-cell ablation and partial pancreatectomy. In the present study, we generated an opposite mouse model with an excessive amount of ectopic β-cells, and analyzed its consequence on β-cell mass and survival. METHODS: Mice underwent sub-renal transplantation (SRT) of pseudo-islets generated from a pancreatic β-cell line MIN6 or intra-pancreatic transplantation (IPT) of MIN6 cells, and morphological and functional changes of their endocrine pancreata were analyzed...
January 7, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29315020/systematic-review-of-islet-cryopreservation
#10
Greg G Kojayan, Michael Alexander, David K Imagawa, Jonathan R T Lakey
Pancreatic islet transplantation is being extensively researched as an alternative treatment for type 1 diabetic patients. This treatment is currently limited by temporal mismatch, between the availability of pancreas and isolated islets from deceased organ donor, and the recipient's need for freshly isolated islets. To solve this issue, cryopreservation of islets may offer the potential to bank islets for transplant on demand. Cryopreservation, however, introduces an overwhelmingly harsh environment to the ever-so-fragile islets...
January 9, 2018: Islets
https://www.readbyqxmd.com/read/29311365/simultaneous-recognition-of-allogeneic-mhc-and-cognate-autoantigen-by-autoreactive-t-cells-in-transplant-rejection
#11
Adam L Burrack, Laurie G Landry, Janet Siebert, Marilyne Coulombe, Ronald G Gill, Maki Nakayama
The autoimmune condition is a primary obstacle to inducing tolerance in type 1 diabetes patients receiving allogeneic pancreas transplants. It is unknown how autoreactive T cells that recognize self-MHC molecules contribute to MHC-disparate allograft rejection. In this report, we show the presence and accumulation of dual-reactive, that is autoreactive and alloreactive, T cells in C3H islet allografts that were transplanted into autoimmune diabetic NOD mice. Using high-throughput sequencing, we discovered that T cells prevalent in allografts share identical TCRs with autoreactive T cells present in pancreatic islets...
January 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29311127/kras-in-organoids
#12
Derek Cheng, David Tuveson
Oncogenic Kras are genetic dependencies for the majority of pancreatic and colorectal adenocarcinomas; however, much remains to be understood regarding its tropism to these carcinomas. Recently developed organoid technology presents a more representative model culture system for pancreatic and colon epithelial tissues as well as better fostering the culture of nonimmortalized cells than two-dimensional culture. These advantages enable cancer researchers to directly compare tumor and normal tissue models to better study tumor initiation as well as therapeutic efficacy...
January 8, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29306997/extracellular-matrix-molecules-and-their-potential-contribution-to-the-function-of-transplanted-pancreatic-islets
#13
REVIEW
L Alberto Llacua, Marijke M Faas, Paul de Vos
Extracellular matrix (ECM) molecules are responsible for structural and biochemical support, as well as for regulation of molecular signalling and tissue repair in many organ structures, including the pancreas. In pancreatic islets, collagen type IV and VI, and laminins are the most abundant molecules, but other ECM molecules are also present. The ECM interacts with specific combinations of integrin α/β heterodimers on islet cells and guides many cellular processes. More specifically, some ECM molecules are involved in beta cell survival, function and insulin production, while others can fine tune the susceptibility of islet cells to cytokines...
January 6, 2018: Diabetologia
https://www.readbyqxmd.com/read/29304344/endogenous-reprogramming-of-alpha-cells-into-beta-cells-induced-by-viral-gene-therapy-reverses-autoimmune-diabetes
#14
Xiangwei Xiao, Ping Guo, Chiyo Shiota, Ting Zhang, Gina M Coudriet, Shane Fischbach, Krishna Prasadan, Joseph Fusco, Sabarinathan Ramachandran, Piotr Witkowski, Jon D Piganelli, George K Gittes
Successful strategies for treating type 1 diabetes need to restore the function of pancreatic beta cells that are destroyed by the immune system and overcome further destruction of insulin-producing cells. Here, we infused adeno-associated virus carrying Pdx1 and MafA expression cassettes through the pancreatic duct to reprogram alpha cells into functional beta cells and normalized blood glucose in both beta cell-toxin-induced diabetic mice and in autoimmune non-obese diabetic (NOD) mice. The euglycemia in toxin-induced diabetic mice and new insulin+ cells persisted in the autoimmune NOD mice for 4 months prior to reestablishment of autoimmune diabetes...
January 4, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29290993/microrna-34c-acts-as-a-bidirectional-switch-in-the-maturation-of-insulin-producing-cells-derived-from-mesenchymal-stem-cells
#15
Chunyu Bai, Yuhua Gao, Xiangyang Zhang, Wancai Yang, Weijun Guan
miRNAs regulate insulin secretion, pancreatic development, and beta-cell differentiation. However, their function in the differentiation of IPCs from MSCs is poorly understood. In this study, to screen for miRNAs and their targets that function during the formation of IPCs from MSCs, we examined the miRNA expression profiles of MSCs and IPCs using RNA-seq and qPCR to confirm the above results. We found that miR-34c exhibited transient upregulation at an early stage of the formation of IPCs derived from MSCs...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29288549/transplantation-of-macro-encapsulated-human-islets-within-the-bioartificial-pancreas-%C3%AE-air-to-patients-with-type-1-diabetes-mellitus
#16
Per-Ola Carlsson, Daniel Espes, Amir Sedigh, Avi Rotem, Baruch Zimermann, Helena Grinberg, Tali Goldman, Uriel Barkai, Yuval Avni, Gunilla T Westermark, Lina Carlbom, Håkan Ahlström, Olof Eriksson, Johan Olerud, Olle Korsgren
Macroencapsulation devices provide the dual possibility to immunoprotect transplanted cells while also being retrievable; the latter bearing importance for safety in future trials with stem-cell derived cells. However, macroencapsulation entails a problem with oxygen supply to the encapsulated cells. The βAir device solves this with an incorporated refillable oxygen tank. This phase 1 study evaluated the safety and efficacy of implanting the βAir device containing allogeneic human pancreatic islets to patients with type 1 diabetes...
December 29, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29287582/acute-pancreatitis-a-rare-but-serious-complication-for-living-liver-donors-risk-factors-and-outcomes
#17
Adil Baskiran, Metin Kement, Bora Barut, Oguzhan Ozsay, Serdar Karakas, Cemalettin Koç, Sezai Yilmaz
OBJECTIVES: The purposes of this study were to determine the incidence of acute pancreatitis after living donor hepatectomy and to investigate potential risk factors and outcomes. MATERIALS AND METHODS: Clinical data of all donors who underwent donor hepatectomy between January 2015 and December 2016 in our liver transplant institute were reviewed. Donor data were obtained from a prospectively maintained database. The donors were divided into 2 groups according to whether they developed postoperative pancreatitis...
December 29, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29284078/hepatobiliary-and-pancreatic-pregnancy-induced-hepatic-veno-occlusive-disease-requiring-liver-transplantation
#18
N Harimoto, K Yugawa, T Ikegami, M Ohira, Y Mano, T Motomura, T Toshima, S Itoh, N Harada, Y Soejima, T Yoshizumi, Y Maehara, Y Oda
No abstract text is available yet for this article.
January 2018: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29277891/fluorescence-and-multispectral-optoacoustic-imaging-for-an-optimised-detection-of-deeply-located-tumours-in-an-orthotopic-mouse-model-of-pancreatic-carcinoma
#19
Joanna Napp, Marieke A Stammes, Jing Claussen, Hendrica A J M Prevoo, Cornelis F M Sier, Freek J M Hoeben, Marc S Robillard, Alexander L Vahrmeijer, Tim Devling, Alan B Chan, Lioe-Fee de Geus-Oei, Frauke Alves
A crucial point for the management of pancreatic ductal adenocarcinoma (PDAC) is the decrease of R1 resections. Our aim was to evaluate the combination of multispectral optoacoustic tomography (MSOT) with fluorescence guided surgery (FGS) for diagnosis and perioperative detection of tumour nodules and resection margins in a xenotransplant mouse model of human pancreatic cancer. The peptide cRGD, conjugated with the near infrared fluorescent (NIRF) dye IRDye800CW and with a trans-cyclooctene (TCO) tag for future click chemistry (cRGD-800CW-TCO), was applied to PDAC bearing immunodeficient nude mice...
December 26, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29276781/recent-progress-in-the-use-and-tracking-of-transplanted-islets-as-a-personalized-treatment-for-type-1-diabetes
#20
Genaro A Paredes-Juarez, Paul de Vos, Jeff W M Bulte
Introduction: Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which the pancreas produces insufficient amounts of insulin. T1DM patients require exogenous sources of insulin to maintain euglycemia. Transplantation of naked or microencapsulated pancreatic islets represents an alternative paradigm to obtain an autonomous regulation of blood glucose levels in a controlled and personalized fashion. However, once transplanted, the fate of these personalized cellular therapeutics is largely unknown, justifying the development of non-invasive tracking techniques...
2017: Expert Review of Precision Medicine and Drug Development
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