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Pancreas cells transplantation

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https://www.readbyqxmd.com/read/29160954/islet-allo-autotransplantation-allogeneic-pancreas-transplantation-followed-by-transplant-pancreatectomy-and-islet-transplantation
#1
M F Nijhoff, J Dubbeld, A R van Erkel, P J M van der Boog, T J Rabelink, M A Engelse, E J P de Koning
Simultaneous pancreas/kidney (SPK) transplantation is an important treatment option for patients with type 1 diabetes (T1D) and end stage renal disease (ESRD). Due to complications, in up to 10% of cases allograft pancreatectomy is necessary shortly after transplantation. Usually the donor pancreas is discarded. Here we report on a novel procedure to rescue endocrine tissue after allograft pancreatectomy. A 39-year-old woman with T1D and ESRD who had received an SPK transplantation required emergency allograft pancreatectomy due to bleeding at the vascular anastomosis...
November 21, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29156810/psc-derived-galectin-1-inducing-epithelial-mesenchymal-transition-of-pancreatic-ductal-adenocarcinoma-cells-by-activating-the-nf-%C3%AE%C2%BAb-pathway
#2
Dong Tang, Jingqiu Zhang, Zhongxu Yuan, Hongpeng Zhang, Yang Chong, Yuqin Huang, Jie Wang, Qingquan Xiong, Sen Wang, Qi Wu, Ying Tian, Yongdie Lu, Xiao Ge, Wenjing Shen, Daorong Wang
Galectin-1 has previously been shown to be strongly expressed in activated pancreatic stellate cells (PSCs) and promote the development and metastasis of pancreatic ductal adenocarcinoma (PDAC). However, the molecular mechanisms by which Galectin-1 promotes the malignant behavior of pancreatic cancer cells remain unclear. In this study, we examined the effects of Galectin-1 knockdown or overexpression in PSCs co-cultured with pancreatic cancer (PANC-1) cells. Immunohistochemical analysis showed expression of epithelial-mesenchymal transition (EMT) markers and MMP9 were positively associated with the expression of Galectin-1 in 66 human PDAC tissues...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29141886/pd-l1-genetic-overexpression-or-pharmacological-restoration-in-hematopoietic-stem-and-progenitor-cells-reverses-autoimmune-diabetes
#3
Moufida Ben Nasr, Sara Tezza, Francesca D'Addio, Chiara Mameli, Vera Usuelli, Anna Maestroni, Domenico Corradi, Silvana Belletti, Luca Albarello, Gabriella Becchi, Gian Paolo Fadini, Christian Schuetz, James Markmann, Clive Wasserfall, Leonard Zon, Gian Vincenzo Zuccotti, Paolo Fiorina
Immunologically based clinical trials performed thus far have failed to cure type 1 diabetes (T1D), in part because these approaches were nonspecific. Because the disease is driven by autoreactive CD4 T cells, which destroy β cells, transplantation of hematopoietic stem and progenitor cells (HSPCs) has been recently offered as a therapy for T1D. Our transcriptomic profiling of HSPCs revealed that these cells are deficient in programmed death ligand 1 (PD-L1), an important immune checkpoint, in the T1D nonobese diabetic (NOD) mouse model...
November 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29123178/a-nanobody-based-tracer-targeting-dpp6-for-non-invasive-imaging-of-human-pancreatic-endocrine-cells
#4
Alexander Balhuizen, Sam Massa, Iris Mathijs, Jean-Valery Turatsinze, Jens De Vos, Stéphane Demine, Catarina Xavier, Olatz Villate, Isabelle Millard, Dominique Egrise, Carmen Capito, Raphaël Scharfmann, Pieter In't Veld, Piero Marchetti, Serge Muyldermans, Serge Goldman, Tony Lahoutte, Luc Bouwens, Decio L Eizirik, Nick Devoogdt
There are presently no reliable ways to quantify endocrine cell mass (ECM) in vivo, which prevents an accurate understanding of the progressive beta cell loss in diabetes or following islet transplantation. To address this unmet need, we coupled RNA sequencing of human pancreatic islets to a systems biology approach to identify new biomarkers of the endocrine pancreas. Dipeptidyl-Peptidase 6 (DPP6) was identified as a target whose mRNA expression is at least 25-fold higher in human pancreatic islets as compared to surrounding tissues and is not changed by proinflammatory cytokines...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29108345/mri-based-evaluation-of-multiorgan-iron-overload-is-a-predictor-of-adverse-outcomes-in-pediatric-patients-undergoing-allogeneic-hematopoietic-stem-cell-transplantation
#5
Natalia Maximova, Massimo Gregori, Giulia Boz, Roberto Simeone, Davide Zanon, Giulia Schillani, Floriana Zennaro
The medical records of 44 pediatric patients who underwent allogeneic transplantation from 2011 to 2015 were retrospectively reviewed. Magnetic resonance imaging was used to measure iron concentrations in the liver, spleen, pancreas and bone. These patients were divided into two groups, 18 with non-elevated (< 100 μmol/g; Group 1) liver iron concentration before transplantation and 26 with elevated (> 100 μmol/g; Group 2) concentration . We compared transplant-related outcomes in the two groups. Iron overload was a negative prognostic risk factor for sinusoidal obstruction syndrome (OR = 17), osteoporosis (OR = 6...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29078330/favorable-outcome-of-experimental-islet-xenotransplantation-without-immunosuppression-in-a-nonhuman-primate-model-of-diabetes
#6
Barbara Ludwig, Stefan Ludwig, Anja Steffen, Yvonne Knauf, Baruch Zimerman, Sophie Heinke, Susann Lehmann, Undine Schubert, Janine Schmid, Martina Bleyer, Uwe Schönmann, Clark K Colton, Ezio Bonifacio, Michele Solimena, Andreas Reichel, Andrew V Schally, Avi Rotem, Uriel Barkai, Helena Grinberg-Rashi, Franz-Josef Kaup, Yuval Avni, Peter Jones, Stefan R Bornstein
Transplantation of pancreatic islets for treating type 1 diabetes is restricted to patients with critical metabolic lability resulting from the need for immunosuppression and the shortage of donor organs. To overcome these barriers, we developed a strategy to macroencapsulate islets from different sources that allow their survival and function without immunosuppression. Here we report successful and safe transplantation of porcine islets with a bioartificial pancreas device in diabetic primates without any immune suppression...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29073149/intrapancreatic-injection-of-human-bone-marrow-derived-mesenchymal-stem-stromal-cells-alleviates-hyperglycemia-and-modulates-the-macrophage-state-in-streptozotocin-induced-type-1-diabetic-mice
#7
Norimitsu Murai, Hirokazu Ohtaki, Jun Watanabe, Zhifang Xu, Shun Sasaki, Kazumichi Yagura, Seiji Shioda, Shoichiro Nagasaka, Kazuho Honda, Masahiko Izumizaki
Type 1 diabetes mellitus is a progressive disease caused by the destruction of pancreatic β-cells, resulting in insulin dependency and hyperglycemia. While transplanted bone marrow-derived mesenchymal stem/stromal cells (BMMSCs) have been explored as an alternative therapeutic approach for diseases, the choice of delivery route may be a critical factor determining their sustainability. This study evaluated the effects of intrapancreatic and intravenous injection of human BMMSCs (hBMMSCs) in streptozotocin (STZ)-induced type 1 diabetic mouse model...
2017: PloS One
https://www.readbyqxmd.com/read/29063316/modeling-of-lymphogenous-and-hematogenous-metastasizing-from-murine-%C3%B0-16-melanoma-in-rats
#8
O I Kit, I V Kaplieva, E M Frantsiyants, L K Trepitaki
We developed a model of experimental melanoma. Intralienal xenogeneic transplantation of a suspension of melanoma cells B16 in physiological saline (0.1 ml; 1:10) was conducted to outbred male rats. In 6 months, histologically confirmed melanoma B16 in the spleen and its metastases in the liver, intestine, pancreas, adrenal glands, and lungs (hematogenous metastasis), as well as in the thymus and lymph nodes (lymphogenous metastasis) were revealed in rats. The proposed rat model of melanoma B16 metastasizes by the hematogenous and lymphogenous pathways, develops over 6 months, and allows receiving sufficient volume of material for analysis...
October 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29051963/applications-of-particulate-oxygen-generating-substances-pogs-in-the-bioartificial-pancreas
#9
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...
November 21, 2017: Biomaterials Science
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
#10
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/29024228/de-novo-hepatocellular-carcinoma-post-multivisceral-transplantation-in-a-child
#11
P Tran, S Zhou, L Wang, M Finegold, L Mascarenas, S Alexopolous, Y Genyk, N Kerkar
De novo hepatocellular carcinoma (HCC) post-transplantation in patients without viral hepatitis is extremely rare, with only three reported adult cases in the English literature. Here, we present a case of de novo HCC that developed in a 7-year-old female, who at 8 months of age received a liver, small bowel, spleen, and pancreas transplantation 6.5 years ago for gastroschisis and total parenteral nutrition (TPN)-related cirrhosis. The post-transplant course was complicated by Epstein-Barr virus (EBV) infection, post-transplant lymphoproliferative disease, and subsequent development of multifocal EBV-associated post-transplant smooth muscle tumors (EBV-PTSMT) in the small bowel 1 year and 10 months after transplantation, respectively...
November 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28984038/beta-cell-replacement-strategies-for-diabetes
#12
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/28977862/identification-and-causes-of-metabonomic-difference-between-orthotopic-and-subcutaneous-xenograft-of-pancreatic-cancer
#13
Bohan Zhan, Shi Wen, Jie Lu, Guiping Shen, Xianchao Lin, Jianghua Feng, Heguang Huang
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors. However, the methodological differences between orthotopic and subcutaneous xenograft (OX and SX) models will cause confusion in understanding its pathological mechanism and clinical relevance. In this study, SX and OX models were established by implanting Panc-1 and BxPC-3 cell strains under skin and on the pancreas of mice, respectively. The tumor tissue and serum samples were collected for(1)H NMR spectroscopy followed by univariate and multivariate statistical analyses...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28975176/deformability-based-microfluidic-separation-of-pancreatic-islets-from-exocrine-acinar-tissue-for-transplant-applications
#14
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 25, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28963457/kinetics-of-functional-beta-cell-mass-decay-in-a-diphtheria-toxin-receptor-mouse-model-of-diabetes
#15
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/28957348/-stealth-dissemination-of-macrophage-tumor-cell-fusions-cultured-from-blood-of-patients-with-pancreatic-ductal-adenocarcinoma
#16
Gary A Clawson, Gail L Matters, Ping Xin, Christopher McGovern, Eric Wafula, Claude dePamphilis, Morgan Meckley, Joyce Wong, Luke Stewart, Christopher D'Jamoos, Naomi Altman, Yuka Imamura Kawasawa, Zhen Du, Loren Honaas, Thomas Abraham
Here we describe isolation and characterization of macrophage-tumor cell fusions (MTFs) from the blood of pancreatic ductal adenocarcinoma (PDAC) patients. The MTFs were generally aneuploidy, and immunophenotypic characterizations showed that the MTFs express markers characteristic of PDAC and stem cells, as well as M2-polarized macrophages. Single cell RNASeq analyses showed that the MTFs express many transcripts implicated in cancer progression, LINE1 retrotransposons, and very high levels of several long non-coding transcripts involved in metastasis (such as MALAT1)...
2017: PloS One
https://www.readbyqxmd.com/read/28951824/intraocular-in%C3%A2-vivo-imaging-of-pancreatic-islet-cell-physiology-pathology
#17
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
https://www.readbyqxmd.com/read/28945308/an-autopsy-based-study-of-trypanosoma-cruzi-persistence-in-organs-of-chronic-chagasic-patients-and-its-relevance-for-transplantation
#18
Luiz A Benvenuti, Alessandra Roggério, Marta M Cavalcanti, Anna S Nishiya, José E Levi
BACKGROUND: Chagas' disease (CD) is caused by infection with the protozoan Trypanosoma cruzi. The disease can affect the heart and/or the gastrointestinal (GI) tract, but around 70% of infected individuals remain asymptomatic in the chronic form. Organ transplantation from T. cruzi-infected donors is often avoided because of the risk of disease transmission, previously reported after heart, kidney, or liver transplantation. METHODS: We investigated by histology, immunohistochemistry and polymerase chain reaction (PCR) the persistence of T...
September 25, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28912479/late-stage-differentiation-of-embryonic-pancreatic-%C3%AE-cells-requires-jarid2
#19
Sara Cervantes, Marta Fontcuberta-PiSunyer, Joan-Marc Servitja, Rebeca Fernandez-Ruiz, Ainhoa García, Lidia Sanchez, Young-Sook Lee, Ramon Gomis, Rosa Gasa
Jarid2 is a component of the Polycomb Repressor complex 2 (PRC2), which is responsible for genome-wide H3K27me3 deposition, in embryonic stem cells. However, Jarid2 has also been shown to exert pleiotropic PRC2-independent actions during embryogenesis. Here, we have investigated the role of Jarid2 during pancreas development. Conditional ablation of Jarid2 in pancreatic progenitors results in reduced endocrine cell area at birth due to impaired endocrine cell differentiation and reduced prenatal proliferation...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28885496/%C3%A3-cell-replacement-therapy-the-next-10-years
#20
Christian Schuetz, Takayuki Anazawa, Sarah E Cross, Leticia Labriola, Raphael P H Meier, Robert R Redfield, Hanne Scholz, Peter G Stock, Nathan W Zammit
ß cell replacement with either pancreas or islet transplantation has progressed immensely over the last decades with current 1- and 5-year insulin independence rates of ~85% and ~50%, respectively. Recent advances are largely attributed to improvements in immunosuppressive regimen, donor selection and surgical technique. However, both strategies are compromised by a scarce donor source. Xenotransplantation provides a potential solution by providing a theoretically unlimited supply of islets, but clinical application has been limited by concerns for a potent immune response against xenogeneic tissue...
September 6, 2017: Transplantation
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