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Pancreas cells transplantation

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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
#1
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/28297573/magnetic-resonance-imaging-guided-delivery-of-neural-stem-cells-into-the-basal-ganglia-of-nonhuman-primates-reveals-a-pulsatile-mode-of-cell-dispersion
#2
Kristen E Malloy, Jinqi Li, Gourav R Choudhury, April Torres, Shruti Gupta, Chris Kantorak, Tim Goble, Peter T Fox, Geoffrey D Clarke, Marcel M Daadi
Optimal stem cell delivery procedures are critical to the success of the cell therapy approach. Variables such as flow rate, suspension solution, needle diameter, cell density, and tissue mechanics affect tissue penetration, backflow along the needle, and the dispersion and survival of injected cells during delivery. Most cell transplantation centers engaged in human clinical trials use custom-designed cannula needles, syringes, or catheters, sometimes precluding the use of magnetic resonance imaging (MRI)-guided delivery to target tissue...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28286566/gastrointestinal-manifestations-of-mitochondrial-disorders-a-systematic-review
#3
REVIEW
Josef Finsterer, Marlies Frank
Mitochondrial disorders (MIDs) due to respiratory-chain defects or nonrespiratory chain defects are usually multisystem conditions [mitochondrial multiorgan disorder syndrome (MIMODS)] affecting the central nervous system (CNS), peripheral nervous system, eyes, ears, endocrine organs, heart, kidneys, bone marrow, lungs, arteries, and also the intestinal tract. Frequent gastrointestinal (GI) manifestations of MIDs include poor appetite, gastroesophageal sphincter dysfunction, constipation, dysphagia, vomiting, gastroparesis, GI pseudo-obstruction, diarrhea, or pancreatitis and hepatopathy...
January 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28280376/single-donor-islet-transplantation-in-type-1-diabetes-patient-selection-and-special-considerations
#4
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
#5
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/28272465/reconstituting-development-of-pancreatic-intraepithelial-neoplasia-from-primary-human-pancreas-duct-cells
#6
Jonghyeob Lee, Emily R Snyder, Yinghua Liu, Xueying Gu, Jing Wang, Brittany M Flowers, Yoo Jung Kim, Sangbin Park, Gregory L Szot, Ralph H Hruban, Teri A Longacre, Seung K Kim
Development of systems that reconstitute hallmark features of human pancreatic intraepithelial neoplasia (PanINs), the precursor to pancreatic ductal adenocarcinoma, could generate new strategies for early diagnosis and intervention. However, human cell-based PanIN models with defined mutations are unavailable. Here, we report that genetic modification of primary human pancreatic cells leads to development of lesions resembling native human PanINs. Primary human pancreas duct cells harbouring oncogenic KRAS and induced mutations in CDKN2A, SMAD4 and TP53 expand in vitro as epithelial spheres...
March 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28272287/risk-factors-and-outcomes-of-de-novo-cancers-excluding-nonmelanoma-skin-cancer-after-liver-transplantation-for-primary-sclerosing-cholangitis
#7
Mohamad A Mouchli, Siddharth Singh, Edward V Loftus, Lisa Boardman, Jayant Talwalkar, Charles B Rosen, Julie K Heimbach, Russell H Wiesner, Bashar Hasan, John J Poterucha, Kymberly D Watt
BACKGROUND: Patients with primary sclerosing cholangitis (PSC) may be at higher of risk of malignancy after liver transplantation (LT) compared to other LT recipients. We aimed to determine the cumulative incidence of/risk factors for and long-term cancer-related mortality in patients with PSC after LT. METHODS: All adult patients who underwent LT for PSC without cholangiocarcinoma from 1984-2012, with follow-up through June 2015. We estimated cumulative incidence, risk factors and mortality from de novo malignancies after LT RESULTS: 293 patients were identified (mean age, 47±12 years; 63...
March 8, 2017: Transplantation
https://www.readbyqxmd.com/read/28255902/imaging-spectrum-of-central-nervous-system-complications-of-hematopoietic-stem-cell-and-solid-organ-transplantation
#8
REVIEW
Andrés Server, Nuria Bargalló, Yngvar Fløisand, Jon Sponheim, Francesc Graus, John K Hald
Neurologic complications are common after hematopoietic stem cell transplantation (HSCT) and solid organ transplantation (SOT) and affect 30-60% of transplant recipients. The aim of this article is to provide a practical imaging approach based on the timeline and etiology of CNS abnormalities, and neurologic complications related to transplantation of specific organs. The lesions will be classified based upon the interval from HSCT procedure: pre-engraftment period <30 days, early post-engraftment period 30-100 days, late post-engraftment period >100 days, and the interval from SOT procedure: postoperative phase 1-4 weeks, early posttransplant syndromes 1-6 months, late posttransplant syndromes >6 months...
March 2, 2017: Neuroradiology
https://www.readbyqxmd.com/read/28252345/evidence-of-stress-in-%C3%AE-cells-obtained-with-laser-capture-microdissection-from-pancreases-of-brain-dead-donors
#9
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/28249332/pancreas-transplantation-delays-the-progression-of-morphological-morphometric-and-ultrastructural-changes-in-testes-of-alloxan-induced-diabetic-rats
#10
César Tadeu Spadella, Amélia Arcângela Teixeira Trindade, Amanda Natália Lucchesi, Célia Sperandéo de Macedo
Aim: The aim of this study was to assess the effects of pancreas transplantation on the progression of testicular lesions in diabetic rats. Methods: Diabetic rats were subjected to pancreas transplantation and sacrificed after 6, 14, 26 and 50 weeks of follow-up, using non-diabetic and untreated diabetic rats as controls. Results: Successful pancreas transplantation corrected all of the metabolic changes observed in diabetic rats, including low levels of testosterone. The testicular mass was decreased, and the relative weight of the testes was high in diabetic rats...
February 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28230643/mtor-inhibition-clinical-transplantation-pancreas-islet
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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