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pancreatic Transplant

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https://www.readbyqxmd.com/read/28432716/deciphering-tacrolimus-induced-toxicity-in-pancreatic-%C3%AE-cells
#1
J Triñanes, A E Rodriguez-Rodriguez, Y Brito, A Wagner, A P J De Vries, G Cuesto, A Acebes, E Salido, A Torres, E Porrini
β-cell transcription factors like: FoxO1, MafA, PDX-1, NeuroD, are dysfunctional in type 2 diabetes (T2DM). PTDM resembles T2DM and reflects interaction between pre-transplant insulin resistance and immunosuppressants, mainly calcineurin inhibitors. We evaluated the effect of tacrolimus, cyclosporine-A and metabolic stressors (glucose+palmitate) on insulinoma β-cells (INS-1) in vitro and in pancreata of obese and lean Zucker rats. Cells were cultured for five days with 100μM palmitate and 22mM glucose; cyclosporin-A (250ng/mL) or tacrolimus (15ng/mL) were added the last 48h...
April 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28423506/granulocyte-colony-stimulating-factor-enhances-the-therapeutic-efficacy-of-bone-marrow-mesenchymal-stem-cell-transplantation-in-rats-with-experimental-acute-pancreatitis
#2
Bo Qu, Yanjie Chu, Fang Zhu, Beibei Wang, Ting Liu, Bo Yu, Shizhu Jin
INTRODUCTION: Acute pancreatitis (AP) is one of the most common diseases involving necrotic inflammation. Bone marrow mesenchymal stem cells (BMMSCs) have the potential of multi-directional differentiation and self-renewal for tissue repair. It remains less clear if granulocyte colony-stimulating factor (G-CSF) can improve the therapeutic effect of BMMSC transplant in AP. Therefore, we explored this issue in a rat model of experimental AP. RESULTS: Transplanted PKH26-positive BMMSCs were present in the injured pancreatic tissue, with some cells co-expressed pancreatic cellular markers, including Pax-4, Ngn3 and Nkx-6...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420418/adult-muscle-derived-stem-cells-engraft-and-differentiate-into-insulin-expressing-cells-in-pancreatic-islets-of-diabetic-mice
#3
Violeta Mitutsova, Wendy Wai Yeng Yeo, Romain Davaze, Celine Franckhauser, El-Habib Hani, Syahril Abdullah, Patrice Mollard, Marie Schaeffer, Anne Fernandez, Ned J C Lamb
BACKGROUND: Pancreatic beta cells are unique effectors in the control of glucose homeostasis and their deficiency results in impaired insulin production leading to severe diabetic diseases. Here, we investigated the potential of a population of nonadherent muscle-derived stem cells (MDSC) from adult mouse muscle to differentiate in vitro into beta cells when transplanted as undifferentiated stem cells in vivo to compensate for beta-cell deficiency. RESULTS: In vitro, cultured MDSC spontaneously differentiated into insulin-expressing islet-like cell clusters as revealed using MDSC from transgenic mice expressing GFP or mCherry under the control of an insulin promoter...
April 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28404865/dual-angiopoietin-2-and-vegfa-inhibition-elicits-antitumor-immunity-that-is-enhanced-by-pd-1-checkpoint-blockade
#4
Martina Schmittnaegel, Nicolò Rigamonti, Ece Kadioglu, Antonino Cassará, Céline Wyser Rmili, Anna Kiialainen, Yvonne Kienast, Hans-Joachim Mueller, Chia-Huey Ooi, Damya Laoui, Michele De Palma
Pathological angiogenesis is a hallmark of cancer and a therapeutic target. Vascular endothelial growth factor A (VEGFA) and angiopoietin-2 (ANGPT2; also known as ANG2) are proangiogenic cytokines that sustain tumor angiogenesis and limit antitumor immunity. We show that combined ANGPT2 and VEGFA blockade by a bispecific antibody (A2V) provided superior therapeutic benefits, as compared to the single agents, in both genetically engineered and transplant tumor models, including metastatic breast cancer (MMTV-PyMT), pancreatic neuroendocrine tumor (RIP1-Tag2), and melanoma...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28397402/micrornas-can-effectively-induce-formation-of-insulin-producing-cells-from-mesenchymal-stem-cells
#5
Chunyu Bai, Yuhua Gao, Xiangchen Li, Kunfu Wang, Hui Xiong, Zhiqiang Shan, Ping Zhang, Wenjie Wang, Weijun Guan, Yuehui Ma
MicroRNAs regulate insulin secretion, pancreatic development and beta cell differentiation. However, the function of microRNAs in the formation of insulin-producing cells (IPCs) from adult stem cells is poorly understood. We examine the microRNA expression profile in nestin-positive umbilical cord-derived mesenchymal stem cells (N-UCMSCs) and nestin-positive pancreatic mesenchymal stem cells using a deep sequencing approach. We also selected specific microRNAs for overexpression in N-UCMSCs and found that miR-375 and miR-26a induced IPCs differentiation from N-UCMSCs by downregulating target genes including mtpn, sox6, bhlhe22 and ccnd1...
April 10, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28397308/improvement-of-isolated-caprine-islet-survival-and-functionality-in-vitro-by-enhancing-of-pdx1-gene-expression
#6
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/28386318/pax4-promotes-pdx1-induced-differentiation-of-mesenchymal-stem-cells-into-insulin-secreting-cells
#7
Lifa Xu, Congjing Xu, Shuping Zhou, Xueke Liu, Jian Wang, Xinkuang Liu, Suping Qian, Yingru Xin, Yi Gao, Yongqiang Zhu, Xiaolong Tang
A shortage of postmortem pancreatic tissue for islet isolation impedes the application of cell replacement therapy in patients with diabetes. As an alternative for islet cell transplantation, transcription factors, including PDX1, PAX4, and neurogenin-3, that aid in the formation of insulin-producing β cells during development have been investigated. The present study evaluated the effects of PAX4 and PDX1 on the differentiation of mesenchymal stem cells (MSCs) into insulin-producing β-like cells in vitro using recombinant adenoviruses carrying PDX1 or PDX1 plus PAX4...
2017: American Journal of Translational Research
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
#8
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
#9
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/28362406/efficient-differentiation-of-pluripotent-stem-cells-to-nkx6-1-pancreatic-progenitors
#10
Emily C McGaugh, M Cristina Nostro
Pluripotent stem cells have the ability to self renew and differentiate to multiple lineages, making them an attractive source for the generation of pancreatic progenitor cells that can be used for the study of and future treatment of diabetes. This article outlines a four-stage differentiation protocol designed to generate pancreatic progenitor cells from human embryonic stem cells (hESCs). This protocol can be applied to a number of human pluripotent stem cell (hPSC) lines. The approach taken to generate pancreatic progenitor cells is to differentiate hESCs to accurately model key stages of pancreatic development...
March 7, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28362046/co-microencapsulation-of-bmscs-and-mouse-pancreatic-%C3%AE-cells-for-improving-the-efficacy-of-type-i-diabetes-therapy
#11
Ruimin Long, Yuangang Liu, Shibin Wang, Li Ye, Peng He
INTRODUCTION: To overcome the shortcomings of pancreas transplantation and insulin injection treatment for type I diabetes, biocompatible materials were used to prepare alginate-chitosan-alginate microcapsules that co-encapsulated bone marrow mesenchymal stem cells and mouse pancreatic β cells to treat diabetic mice. METHODS: Blank alginate-chitosan-alginate (ACA) microcapsules and co-microencapsulated cells were prepared using a high-voltage electrostatic method and then characterized using an inverted microscope...
March 21, 2017: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/28360408/senescence-of-pancreas-in-middle-aged-rats-with-normal-vascular-function
#12
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
#13
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/28358727/salvage-islet-auto-transplantation-after-relaparatomy
#14
Gianpaolo Balzano, Rita Nano, Paola Maffi, Alessia Mercalli, Raffaelli Melzi, Francesca Aleotti, Francesca Gavazzi, Cesare Berra, Francesco De Cobelli, Massimo Venturini, Paola Magistretti, Marina Scavini, Giovanni Capretti, Alessandro Del Maschio, Antonio Secchi, Alessandro Zerbi, Massimo Falconi, Lorenzo Piemonti
BACKGROUND: To assess feasibility, safety and metabolic outcome of islet auto transplantation (IAT) in patients undergoing completion pancreatectomy because of sepsis or bleeding following pancreatic surgery. METHODS: From November 2008 to October 2016, 22 patients were candidates to salvage IAT during emergency relaparotomy because of postpancreatectomy sepsis (n=11) or bleeding (n=11). Feasibility, efficacy, and safety of salvage IAT were compared to those documented in a cohort of 36 patients who were candidate to simultaneous IAT during nonemergency preemptive completion pancreatectomy through the pancreaticoduodenectomy...
March 29, 2017: Transplantation
https://www.readbyqxmd.com/read/28351620/oxygenated-thawing-and-rewarming-alleviate-rewarming-injury-of-cryopreserved-pancreatic-islets
#15
Hirotake Komatsu, Alyssa Barriga, Leonard Medrano, Keiko Omori, Fouad Kandeel, Yoko Mullen
BACKGROUND/AIMS: Pancreatic islet transplantation is an effective treatment for Type 1 diabetic patients to eliminate insulin injections; however, a shortage of donor organs hinders the widespread use. Although long-term islet storage, such as cryopreservation, is considered one of the key solutions, transplantation of cryopreserved islets is still not practical due to the extensive loss during the cryopreservation-rewarming process. We have previously reported that culturing islets in a hyperoxic environment is an effective treatment to prevent islet death from the hypoxic injury during culture...
March 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28350292/rescue-arterial-revascularization-using-cryopreserved-iliac-artery-allograft-in-liver-transplant-patients
#16
Kayvan Mohkam, Benjamin Darnis, Agnès Rode, Nathalie Hetsch, Gregorio Balbo, Jean-Paul Bourgeot, Salim Mezoughi, Hassan Demian, Christian Ducerf, Jean-Yves Mabrut
OBJECTIVES: Management of hepatic arterial complications after liver transplant remains challenging. The aim of our study was to assess the efficacy of rescue arterial revascularization using cryopreserved iliac artery allografts in this setting. MATERIALS AND METHODS: Medical records of patients with liver transplants who underwent rescue arterial revascularization using cryopreserved iliac artery allografts at a single institution were reviewed. RESULTS: From 1992 to 2015, 7 patients underwent rescue arterial revascularization using cryopreserved iliac artery allografts for hepatic artery pseudoaneurysm (3 patients), thrombosis (2 patients), aneurysm (1 patient), or stenosis (1 patient)...
March 28, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28349071/forkhead-protein-foxo1-acts-as-a-repressor-to-inhibit-cell-differentiation-in-human-fetal-pancreatic-progenitor-cells
#17
Zongzhe Jiang, Jingjing Tian, Wenjian Zhang, Hao Yan, Liping Liu, Zhenhe Huang, Jinning Lou, Xiaosong Ma
Our colleagues have reported previously that human pancreatic progenitor cells can readily differentiate into insulin-containing cells. Particularly, transplantation of these cell clusters upon in vitro induction for 3-4 w partially restores hyperglycemia in diabetic nude mice. In this study, we used human fetal pancreatic progenitor cells to identify the forkhead protein FoxO1 as the key regulator for cell differentiation. Thus, induction of human fetal pancreatic progenitor cells for 1 week led to increase of the pancreatic β cell markers such as Ngn3, but decrease of stem cell markers including Oct4, Nanog, and CK19...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28342320/mitigating-hypoxic-stress-on-pancreatic-islets-via-in-situ-oxygen-generating-biomaterial
#18
Maria M Coronel, Ryan Geusz, Cherie L Stabler
A major obstacle in the survival and efficacy of tissue engineered transplants is inadequate oxygenation, whereby unsupportive oxygen tensions result in significant cellular dysfunction and death within the implant. In a previous report, we developed an innovative oxygen generating biomaterial, termed OxySite, to provide supportive in situ oxygenation to cells and prevent hypoxia-induced damage. Herein, we explored the capacity of this biomaterial to mitigate hypoxic stress in both rat and nonhuman primate pancreatic islets by decreasing cell death, supporting metabolic activity, sustaining aerobic metabolism, preserving glucose responsiveness, and decreasing the generation of inflammatory cytokines...
June 2017: Biomaterials
https://www.readbyqxmd.com/read/28341510/endovascular-stenting-of-portal-vein-for-graft-rescue-after-a-pancreas-transplant-venous-graft-thrombosis-a-case-report
#19
Ossama M Reslan, Jordan M Kirsch, Hitesh Kaul, Stalin Campos, Radi Zaki, Paul S Brady, Kamran Khanmoradi
Venous thrombosis of pancreas transplant allografts often leads to graft loss. Its worrisome complication and difficult to treat, forming the most common nonimmunological cause of graft loss. Multiple risk factors have been implicated in the development of venous thrombosis of pancreas transplant. Color Doppler ultrasonography (CDUS) enables early diagnosis of venous thrombosis, thus increasing the possibility of graft-rescue treatments. Endovascular management of pancreatic transplant vascular complications are scant and in the form of case reports...
March 21, 2017: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/28340694/composition-and-organization-of-the-pancreatic-extracellular-matrix-by-combined-methods-of-immunohistochemistry-proteomics-and-scanning-electron-microscopy
#20
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
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