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Pancreas cells transplantation

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https://www.readbyqxmd.com/read/28230643/mtor-inhibition-clinical-transplantation-pancreas-islet
#1
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
#2
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/28174674/the-evaluation-of-islet-purification-methods-that-use-large-bottles-to-create-a-continuous-density-gradient
#3
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
https://www.readbyqxmd.com/read/28164137/immune-responses-to-tissue-restricted-nonmajor-histocompatibility-complex-antigens-in-allograft-rejection
#4
REVIEW
Ankit Bharat, T Mohanakumar
Chronic diseases that result in end-stage organ damage cause inflammation, which can reveal sequestered self-antigens (SAgs) in that organ and trigger autoimmunity. The thymus gland deletes self-reactive T-cells against ubiquitously expressed SAgs, while regulatory mechanisms in the periphery control immune responses to tissue-restricted SAgs. It is now established that T-cells reactive to SAgs present in certain organs (e.g., lungs, pancreas, and intestine) are incompletely eliminated, and the dysregulation of peripheral immuneregulation can generate immune responses to SAgs...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28150744/engineering-an-endocrine-neo-pancreas-by-repopulation-of-a-decellularized-rat-pancreas-with-islets-of-langerhans
#5
H Napierala, K-H Hillebrandt, N Haep, P Tang, M Tintemann, J Gassner, M Noesser, H Everwien, N Seiffert, M Kluge, E Teegen, D Polenz, S Lippert, D Geisel, A Reutzel Selke, N Raschzok, A Andreou, J Pratschke, I M Sauer, B Struecker
Decellularization of pancreata and repopulation of these non-immunogenic matrices with islets and endothelial cells could provide transplantable, endocrine Neo- Pancreata. In this study, rat pancreata were perfusion decellularized and repopulated with intact islets, comparing three perfusion routes (Artery, Portal Vein, Pancreatic Duct). Decellularization effectively removed all cellular components but conserved the pancreas specific extracellular matrix. Digital subtraction angiography of the matrices showed a conserved integrity of the decellularized vascular system but a contrast emersion into the parenchyma via the decellularized pancreatic duct...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28135283/the-spleen-is-an-ideal-site-for-inducing-transplanted-islet-graft-expansion-in-mice
#6
Takeshi Itoh, Hitomi Nishinakamura, Kenjiro Kumano, Hiroyuki Takahashi, Shohta Kodama
Alternative islet transplantation sites have the potential to reduce the marginal number of islets required to ameliorate hyperglycemia in recipients with diabetes. Previously, we reported that T cell leukemia homeobox 1 (Tlx1)+ stem cells in the spleen effectively regenerated into insulin-producing cells in the pancreas of non-obese diabetic mice with end-stage disease. Thus, we investigated the spleen as a potential alternative islet transplantation site. Streptozotocin-induced diabetic C57BL/6 mice received syngeneic islets into the portal vein (PV), beneath the kidney capsule (KC), or into the spleen (SP)...
2017: PloS One
https://www.readbyqxmd.com/read/28130838/production-of-high-quality-islets-from-goettingen-minipigs-choice-of-organ-preservation-solution-donor-pool-and-optimal-cold-ischemia-time
#7
Anja Steffen, Thomas Kiss, Janine Schmid, Undine Schubert, Sophie Heinke, Susann Lehmann, Stefan Bornstein, Barbara Ludwig, Stefan Ludwig
BACKGROUND: The transplantation of porcine islets into man might soon become reality for patients with type 1 diabetes mellitus. Therefore, porcine islets of high quality and quantity, and a scalable isolation process with strict quality control will be an unconditional prerequisite to enable the best possible transplantation graft. In this study, we provide a comparative study evaluating islet isolation outcome and in vitro survival based upon donor age, organ preservation solution (OPS), and cold ischemia time (CIT)...
January 28, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28101160/facile-mechanical-shaking-method-is-an-improved-isolation-approach-for-islet-preparation-and-transplantation
#8
Nina Yin, Tao Chen, Yuling Yu, Yongming Han, Fei Yan, Zhou Zheng, Zebin Chen
Successful islet isolation is crucial for islet transplantation and cell treatment for type 1 diabetes. Current isolation methods are able to obtain 500-1,000 islets per rat, which results in a waste of ≥50% of total islets. In the present study, a facile mechanical shaking method for improving islet yield (up to 1,500 per rat) was developed and summarized, which was demonstrated to be more effective than the existing well-established stationary method. The present results showed that isolated islets have a maximum yield of 1,326±152 when shaking for 15 min for the fully-cannulated pancreas...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28092668/upregulation-of-ret-induces-perineurial-invasion-of-pancreatic-adenocarcinoma
#9
M Amit, S Na'ara, L Leider-Trejo, Y Binenbaum, N Kulish, E Fridman, A Shabtai-Orbach, R J Wong, Z Gil
Tumor spread along nerves, a phenomenon known as perineurial invasion, is common in various cancers including pancreatic ductal adenocarcinoma (PDAC). Neural invasion is associated with poor outcome, yet its mechanism remains unclear. Using the transgenic Pdx-1-Cre/KrasG12D /p53R172H (KPC) mouse model, we investigated the mechanism of neural invasion in PDAC. To detect tissue-specific factors that influence neural invasion by cancer cells, we characterized the perineurial microenvironment using a series of bone marrow transplantation (BMT) experiments in transgenic mice expressing single mutations in the Cx3cr1, GDNF and CCR2 genes...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28017506/insulin-producing-cells-generation-by-overexpression-of-mir-375-in-adipose-derived-mesenchymal-stem-cells-from-diabetic-patients
#10
Mehran Piran, Seyed Ehsan Enderami, Mehrdad Piran, Hadis Soltani Sedeh, Ehsan Seyedjafari, Abdolreza Ardeshirylajimi
Diabetes Mellitus (DM) is a systematic disease, which happens because of destruction of islets of Langerhans in the pancreas and systematic resistance to insulin. The lack of donor for pancreas transplantation and risk of transplant rejection is the main challenge in the treatment of this disease. Stem cells are proper and sufficient source for creating insulin-producing cells (IPC). In this study adipose tissue was provided from diabetic patients operated for liposuction and then adipose derived stem cells (ADSCs) were isolated, characterized and then treated by lentiviruses containing miR-375, after 7, 14 and 21 days of induction, islet-like clusters (ILC) specific genes including insulin and PDX1 were evaluated by Real Time RT-PCR...
December 22, 2016: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/28008169/advances-in-islet-encapsulation-technologies
#11
REVIEW
Tejal Desai, Lonnie D Shea
Type 1 diabetes is an autoimmune disorder in which the immune system attacks and destroys insulin-producing islet cells of the pancreas. Although islet transplantation has proved to be successful for some patients with type 1 diabetes, its widespread use is limited by islet donor shortage and the requirement for lifelong immunosuppression. An encapsulation strategy that can prevent the rejection of xenogeneic islets or of stem cell-derived allogeneic islets can potentially eliminate both of these barriers. Although encapsulation technology has met several challenges, the convergence of expertise in materials, nanotechnology, stem cell biology and immunology is allowing us to get closer to the goal of encapsulated islet cell therapy for humans...
December 23, 2016: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/27931513/immunogenicity-of-anti-hla-antibodies-in-pancreas-and-islet-transplantation
#12
Benjamin Chaigne, Kirsten Geneugelijk, Benot Bdat, Mohamed Alibashe Ahmed, Gideon Hnger, Sophie de Seigneux, Sandrine Demuylder-Mischler, Thierry Berney, Eric Spierings, Sylvie Ferrari-Lacraz, Jean Villard
The aim of the current study was to characterize the anti-HLA antibodies before and after pancreatic islet or pancreas transplantation. We assessed the risk of anti-donor-specific antibody (DSA) sensitization in a single-center, retrospective clinical study at Geneva University Hospital. Data regarding clinical characteristics, graft outcome, HLA mismatch, donor HLA immunogenicity, and anti-HLA antibody characteristics were collected. Between January 2008 and July 2014, 18 patients received islet transplants, and 26 patients received a pancreas transplant...
November 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27930567/granulocytic-sarcoma-of-the-pancreas-on-18f-fdg-pet-ct-a-case-report
#13
Akira Ishii, Tadakazu Kondo, Tomomi Oka, Yuji Nakamoto, Akifumi Takaori-Kondo
RATIONALE: Granulocytic sarcoma (GS) is defined as leukemia infiltration in any organ other than the bone marrow. GS rarely occurs in the pancreas. Here, we present the first report of GS in the pancreas on F-fluorodexyglucose positron emission tomography/computed tomography (F-FDG PET/CT). PATIENT CONCERNS: A 19-year-old male patient with acute myeloid leukemia received a human leukocyte antigen-haploidentical stem cell transplant as a second transplant while in second complete remission...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27925870/hydrogen-sulfide-enhances-pancreatic-%C3%AE-cell-differentiation-from-human-tooth-under-normal-and-glucotoxic-conditions
#14
Ioan Valentin Matei, Hisataka Ii, Ken Yaegaki
AIM: Glucotoxicity obstructs pancreatic differentiation from adult stem cells. The aim was to develop a novel protocol for differentiation of dental pulp stem cells (DPSCs) into pancreatic β cells and determine the effect of H2S on glucotoxicity. MATERIALS & METHODS: DPSCs were differentiated with media containing 5.5 or 25.0 mM glucose, exposed to 1 ng/ml H2S. Glucotoxicity, expression of β-cell markers, INS, PDX1 and GLUT2, and PI3K/AKT pathway were assessed...
December 7, 2016: Regenerative Medicine
https://www.readbyqxmd.com/read/27888562/parainfluenza-3-infections-early-after-kidney-or-simultaneous-pancreas-kidney-transplantation
#15
Ilkka Helanterä, Veli-Jukka Anttila, Raisa Loginov, Marko Lempinen
Parainfluenza (PIV) can cause serious infections after hematopoietic stem cell or lung transplantation. Limited data exist about PIV infections after kidney transplantation. We describe an outbreak of PIV-3 in a transplant unit. During the outbreak 45 patients were treated on the ward for postoperative care after kidney or simultaneous pancreas-kidney (SPK) transplantation. Altogether 29 patients were tested for respiratory viruses (12 patients with respiratory symptoms, 17 asymptomatic exposed patients) from nasopharyngeal swabs with PCR...
November 26, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27862883/the-banff-2015-kidney-meeting-report-current-challenges-in-rejection-classification-and-prospects-for-adopting-molecular-pathology
#16
A Loupy, M Haas, K Solez, L Racusen, D Glotz, D Seron, B J Nankivell, R B Colvin, M Afrouzian, E Akalin, N Alachkar, S Bagnasco, J U Becker, L Cornell, C Drachenberg, D Dragun, H de Kort, I W Gibson, E S Kraus, C Lefaucheur, C Legendre, H Liapis, T Muthukumar, V Nickeleit, B Orandi, W Park, M Rabant, P Randhawa, E F Reed, C Roufosse, S V Seshan, B Sis, H K Singh, C Schinstock, A Tambur, A Zeevi, M Mengel
The XIII Banff meeting, held in conjunction the Canadian Society of Transplantation in Vancouver, Canada, reviewed the clinical impact of updates of C4d-negative antibody-mediated rejection (ABMR) from the 2013 meeting, reports from active Banff Working Groups, the relationships of donor-specific antibody tests (anti-HLA and non-HLA) with transplant histopathology, and questions of molecular transplant diagnostics. The use of transcriptome gene sets, their resultant diagnostic classifiers, or common key genes to supplement the diagnosis and classification of rejection requires further consensus agreement and validation in biopsies...
January 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/27842980/establishment-characterization-and-long-term-culture-of-human-endocrine-pancreas-derived-microvascular-endothelial-cells
#17
Valeria Sordi, Anna Ferri, Valentina Ceserani, Emilio Ciusani, Erica Dugnani, Silvia Pellegrini, Rita Nano, Lorenza Pecciarini, Augusto Pessina, Luisa Pascucci, Lorenzo Piemonti, Giulio Alessandri
BACKGROUND: In vitro primary cultures of microvascular endothelial cells from endocrine pancreas are difficult to obtain, but can be a very helpful tool for studies of islet biology, transplantation and regenerative medicine. METHODS: We applied a protocol recently described for the isolation and culture of brain microvascular endothelial cells (EC) on human pancreatic islets. EC obtained were characterized in terms of morphological (light and transmission electron microscopy), phenotypical (by immunofluorescence and flow cytometry) and functional (cord formation assay and protein secretion by multiplex bead-based assay) characteristics...
January 2017: Cytotherapy
https://www.readbyqxmd.com/read/27836003/adult-human-pancreas-derived-cells-expressing-stage-specific-embryonic-antigen-4-differentiate-into-sox9-expressing-and-ngn3-expressing-pancreatic-ducts-in-vivo
#18
Song Lee, Chan Mi Lee, Song Cheol Kim
BACKGROUND: Tissue-specific stem/progenitor cells are found in various adult tissues and may have the capacity for lineage-specific differentiation, facilitating applications in autologous transplantation. Stage-specific embryonic antigen 4 (SSEA-4), an early embryonic glycolipid antigen, is expressed in cells derived from adult human pancreas exocrine tissue. Here, we examined the characteristics and lineage-specific differentiation capacity of SSEA-4(+) cells. METHODS: Human adult partial pancreas tissues were obtained from different donors and cultured in vitro...
November 11, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27833043/efficient-generation-of-pancreatic-%C3%AE-like-cells-from-the-mouse-gallbladder
#19
Yuhan Wang, Feorillo Galivo, Carl Pelz, Annelise Haft, Jonghyeob Lee, Seung K Kim, Markus Grompe
Direct reprogramming is a promising approach for the replacement of β cells in diabetes. Reprogramming of cells originating from the endodermal lineage, such as acinar cells in the pancreas, liver cells and gallbladder cells has been of particular interest because of their developmental proximity to β cells. Our previous work showed that mouse gallbladder epithelium can be partially reprogrammed in vitro to generate islet-like cells (rGBC1). Here, the reprogramming protocol was substantially improved, yielding cells (rGBC2) closer to functional β cells than the 1st generation method with higher conversion efficiency and insulin expression...
November 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27823612/islet-cell-transplantation-and-alternative-therapies
#20
REVIEW
Betul Hatipoglu
Even though type 2 diabetes rates plateaued, type 1 diabetes continues to increase. Pancreas transplantation is a treatment modality for patients who suffer hypoglycemic unawareness or complications from diabetes. Islet cell transplantation success rates have improved with modification and advances in isolation, transplantation, and new immunosuppression regimens. The new cell sources as well as delivery ways are explored and being tested in human trials.
December 2016: Endocrinology and Metabolism Clinics of North America
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