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Islet transplant

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https://www.readbyqxmd.com/read/29241367/differentiation-of-conjunctiva-mesenchymal-stem-cells-into-secreting-islet-beta-cells-on-plasma-treated-electrospun-nanofibrous-scaffold
#1
Samad Nadri, Ghasem Barati, Hossein Mostafavi, Abdolreza Esmaeilzadeh, Seyed Ehsan Enderami
Transplantation of stem cells using biocompatible nanofibrous scaffolds is a promising therapeutic method for treating Diabetic Mellitus. The aim of this study was to derive insulin-producing cells (IPCs) from conjunctiva-derived mesenchymal stem cell (CJMSCs) and to compare the functionality of differentiated IPCs in a three-dimensional (3D) culture with 2D. Furthermore, the effects of hydrophobicity of scaffold on IPCs differentiation were examined. Scanning electron microscopy (SEM), quantitative real times PCR (qPCR), Immunostaining and flow cytometry were used to analyze fabricated scaffold and the presence of IPCs...
December 14, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29236782/interleukin-35-mitigates-the-function-of-murine-transplanted-islet-cells-via-regulation-of-treg-th17-ratio
#2
Yin Zongyi, Zou Funian, Li Hao, Wang Xin, Cheng Ying, Zhang Jialin, Liu Yongfeng, Li Baifeng
Pancreatic islet transplantation is a promising treatment for type 1 diabetes (T1D). Interleukin-35 (IL-35) is a recently discovered cytokine that exhibits potent immunosuppressive functions. However, the role of IL-35 in islet transplant rejection remains to be elucidated. In this study, we isolated islet cells of BALB/c mouse and purified CD4+ T cell subsets of a C57BL/6 mouse. The model for islet transplantation was established in vitro by co-culture of the islet cells and CD4+ T cells. IL-35 (20 ng/ml) was administered every other day...
2017: PloS One
https://www.readbyqxmd.com/read/29230944/improved-insulin-sensitivity-appears-to-remain-for-a-mean-of-four-years-following-islet-cell-transplant-for-type-1-diabetes
#3
Brett Rydzon, Rebecca S Monson, Jose Oberholzer, Krista A Varady, Melena D Bellin, Kirstie K Danielson
BACKGROUND: Impaired insulin sensitivity (IS) predicts complications and mortality in type 1 diabetes (T1D). IS improves shortly after islet cell transplant for type 1 diabetes, yet long-term changes in IS, and associated factors such as patient characteristics, transplant factors, clinical management, and IS-related biomarkers are unknown. METHODS: Up to nine years (mean four) of longitudinal data were available on 22 adults (18 female) with T1D who received 1-3 transplants in Phase 1/2 or 3 clinical trials (2004-2014)...
December 12, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29228112/xenotransplantation-the-current-status-and-prospects
#4
D K C Cooper, R Gaston, D Eckhoff, J Ladowski, T Yamamoto, L Wang, H Iwase, H Hara, M Tector, A J Tector
Introduction: There is a continuing worldwide shortage of organs from deceased human donors for transplantation into patients with end-stage organ failure. Genetically engineered pigs could resolve this problem, and could also provide tissues and cells for the treatment of conditions such as diabetes, Parkinson's disease and corneal blindness. Sources of data: The current literature has been reviewed. Areas of agreement: The pathobiologic barriers are now largely defined...
December 8, 2017: British Medical Bulletin
https://www.readbyqxmd.com/read/29222788/rat-pancreatic-beta-cell-culture
#5
Myrian Velasco, Carlos Larqué, Carlos Manlio Díaz-García, Carmen Sanchez-Soto, Marcia Hiriart
In this chapter, we describe the methods used to culture mainly rat pancreatic beta cells. We consider necessary to use this approach to get more information about physiological, biophysical, and molecular biology characteristics of primary beta cells. Most of the literature published has been developed in murine and human beta-cell lines. However, there are many differences between tumoral cell lines and native cells because, in contrast to cell lines, primary cells do not divide. Moreover, cell lines can be in various stages of the cell cycle and thus have a different sensitivity to glucose, compared to primary cells...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29218834/comparative-evaluation-of-simple-indices-using-a-single-fasting-blood-sample-to-estimate-beta-cell-function-after-islet-transplantation
#6
Justyna E Gołębiewska, Julia Solomina, Celeste Thomas, Mark Kijek, Piotr Bachul, Lindsay Basto, Karolina Golab, Ling-Jia Wang, Natalie Fillman, Martin Tibudan, Kamil Cieply, Luis Philipson, Alicja Dębska-Ślizień, J Michael Millis, John Fung, Piotr Witkowski
Six single fasting blood sample based indices: Secretory Unit of Islet Transplant Objects (SUITO), Transplant Estimated Function (TEF), Homeostasis Model Assessment (HOMA)2-B%, C-peptide/glucose ratio (CP/G), C-peptide/glucose creatinine ratio (CP/GCr) and BETA-2 score, were compared against commonly used 90-min mixed meal tolerance test (MMTT) serum glucose and beta-score to assess which of them best recognizes the state of acceptable blood glucose control without insulin supplementation after islet allotransplantation (ITx)...
December 8, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29215800/microencapsulation-for-the-cell-therapy-of-type-1-diabetes-mellitus-the-interplay-between-common-beliefs-prejudices-and-real-progress
#7
EDITORIAL
Riccardo Calafiore
When Anthony Sun (1) showed, for the first time in 1980, that intraperitoneal graft of allogeneic rat pancreatic islet containing alginate-poly-L-lysine microcapsules, reversed hyperglycemia in not immunosuppressed diabetic rats, a new era for the cell therapy of diabetes had started. As a unique and unmatched result, years later, Sun replied success in diabetic primates, that upon intraperitoneal transplant of microencapsulated porcine islets, showed long-term remission of hyperglycemia. However, at that time, the international academic and scientific community greeted with skepticism such a revolutionary approach...
December 7, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29212608/clinical-islet-transplantation-for-type-1-diabetes-in-canada-referral-patterns-and-eligibility-assessment
#8
Ying Ling, Aashna Gill, Richard Oram, A M James Shapiro, Peter Senior
OBJECTIVES: Careful selection for clinical islet transplantation (CIT) is required because of limited organ supply and the risks for lifelong immunosuppression. However, the indications for this novel treatment may not be widely known, and selection criteria continue to evolve. We sought to describe the pattern of referrals to our centre and the most common factors determining eligibility for CIT. METHODS: We performed a retrospective chart review of all applications for CIT received at the University of Alberta between May 2009 and April 2012...
December 4, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/29210476/delayed-revascularization-of-islets-after-transplantation-by-il-6-blockade-in-pig-to-non-human-primate-islet-xenotransplantation-model
#9
Byoung-Hoon Min, Jun-Seop Shin, Jong-Min Kim, Seong-Jun Kang, Hyun-Je Kim, Il-Hee Yoon, Su-Kyoung Park, Ji-Won Choi, Min-Suk Lee, Chung-Gyu Park
BACKGROUND: Pancreatic islet transplantation is currently proven as a promising treatment for type 1 diabetes patients with labile glycemic control and severe hypoglycemia unawareness. Upon islet transplantation, revascularization is essential for proper functioning of the transplanted islets. As IL-6 is important for endothelial cell survival and systemic inflammation related to xenograft, the effect of IL-6 receptor antagonist, tocilizumab, on revascularization of the transplanted islets was examined in pig to non-human primate islet xenotransplantation model...
December 6, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29208633/in-vivo-visualization-of-beta-cells-by-targeting-of-gpr44
#10
Olof Eriksson, Peter Johnström, Zsolt Cselenyi, Mahabuba Jahan, Ram K Selvaraju, Marianne Jensen-Waern, Akihiro Takano, Maria Sörhede Winzell, Christer Halldin, Stanko Skrtic, Olle Korsgren
GPR44 expression has recently been described as highly beta cell selective in the human pancreas and constitutes a tentative surrogate imaging biomarker in diabetes.A radiolabeled small molecule GPR44 antagonist, [11C]AZ12204657, was evaluated for visualization of beta cells in pigs and non-human primates by Positron Emission Tomography (PET) as well as in immunodeficient mice transplanted with human islets under the kidney capsule. In vitro autoradiography of human and animal pancreatic sections from non-diabetic and diabetic subjects, in combination with insulin staining, was performed to assess beta cell selectivity of the radiotracer...
December 5, 2017: Diabetes
https://www.readbyqxmd.com/read/29203613/nfe2l1-silenced-insulinoma-cells-acquire-aggressiveness-and-chemo-resistance
#11
Jingqi Fu, Hongzhi Zheng, Qi Cui, Chengjie Chen, Simeng Bao, Jing Sun, Lu Li, Bei Yang, Huihui Wang, Yongyong Hou, Yuanyuan Xu, Yuanhong Xu, Qiang Zhang, Jingbo Pi
The transcription factor nuclear factor erythroid 2 like 1 (NFE2L1 or NRF1) is involved in various critical cell processes such as maintenance of ubiquitin-proteasome system and regulation of the cellular antioxidant response. We previously determined that pancreatic β-cell-specific Nfe2l1-knockout mice had hyperinsulinemia, and that silencing of Nfe2l1 in mouse islets or MIN6 insulinoma β-cells induced elevated basal insulin release and altered glucose metabolism. Hypoglycemia is a major issue with aggressive insulinomas, although a role of NFE2L1 in this pathology is not defined...
December 4, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29202467/endothelial-chimerism-and-vascular-sequestration-protect-pancreatic-islet-grafts-from-antibody-mediated-rejection
#12
Chien-Chia Chen, Eric Pouliquen, Alexis Broisat, Francesco Andreata, Maud Racapé, Patrick Bruneval, Laurence Kessler, Mitra Ahmadi, Sandrine Bacot, Carole Saison-Delaplace, Marina Marcaud, Jean-Paul Duong Van Huyen, Alexandre Loupy, Jean Villard, Sandrine Demuylder-Mischler, Thierry Berney, Emmanuel Morelon, Meng-Kun Tsai, Marie-Nathalie Kolopp-Sarda, Alice Koenig, Virginie Mathias, Stéphanie Ducreux, Catherine Ghezzi, Valerie Dubois, Antonino Nicoletti, Thierry Defrance, Olivier Thaunat
Humoral rejection is the most common cause of solid organ transplant failure. Here, we evaluated a cohort of 49 patients who were successfully grafted with allogenic islets and determined that the appearance of donor-specific anti-HLA antibodies (DSAs) did not accelerate the rate of islet graft attrition, suggesting resistance to humoral rejection. Murine DSAs bound to allogeneic targets expressed by islet cells and induced their destruction in vitro; however, passive transfer of the same DSAs did not affect islet graft survival in murine models...
November 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29198674/external-validation-of-the-newly-developed-beta-2-scoring-system-for-pancreatic-islet-graft-function-assessment
#13
J Gołębiewska, J Solomina, M R Kijek, A Kotukhov, L Basto, K Gołąb, P J Bachul, E Konsur, K Ciepły, N Fillman, L-J Wang, C C Thomas, L H Philipson, M Tibudan, A Krenc, A Dębska-Ślizień, J Fung, P Witkowski
BACKGROUND: BETA-2 score using a single fasting blood sample was developed to estimate beta-cell function after islet transplantation (ITx) and was validated internally by a high ITx volume center (Edmonton). The goal was to validate BETA-2 externally, in our center. METHODS: Areas under receiver operating characteristic curves (AUROCs) were obtained to see if beta score or BETA-2 would better detect insulin independence and glucose intolerance. RESULTS: We analyzed values from 48 mixed meal tolerance tests (MMTTs) in 4 ITx recipients with a long-term follow-up to 140 months (LT group) and from 54 MMTTs in 13 short-term group patients (ST group)...
December 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29198672/hypoxia-induced-damage-in-human-islets-is-reduced-with-the-use-of-mesenchymal-stem-cell-preconditioned-medium
#14
D Brandhorst, H Brandhorst, S Acreman, S W Schive, H Bjørnson Scholz, P R V Johnson
BACKGROUND: Mesenchymal stem cells (MSCs) are protective for islets when cotransplanted in a hypoxic environment. However, the risk of neoplasia is increased when MSCs are transplanted into immunosuppressed patients. This initial study aimed to investigate whether the production of protective factors from MSC can be stimulated by different culture conditions to benefit human islets cultured in hypoxia. METHODS: MSC were isolated from human adipose tissue and cultured for 2 days in supplemented Minimum Essential Media α (MEMα) and 21% (21%-MEMα) or 1% oxygen (1%-MEMα)...
December 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29198671/effect-of-etanercept-concentration-on-human-islet-integrity
#15
S Acreman, H Brandhorst, A Abraham, P R V Johnson, D Brandhorst
BACKGROUND: Etanercept is widely used as an antiinflammatory drug to improve engraftment after intraportal islet transplantation. In contrast to other immunosuppressive agents, very little is known about detrimental effects of etanercept on islets. The aim of this pilot study was to define the toxic range of etanercept. METHODS: Human islets isolated from 8 donors were cultured for 4-5 days at 37°C in culture medium supplemented with etanercept at concentrations from 2...
December 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/29190258/age-and-early-graft-function-relate-with-risk-benefit-ratio-of-allogenic-islet-transplantation-under-antithymocyte-globulin-mycophenolate-mofetil-tacrolimus-immune-suppression-erratum
#16
https://www.readbyqxmd.com/read/29178588/early-barriers-to-neonatal-porcine-islet-engraftment-in-a-dual-transplant-model
#17
K P Samy, R P Davis, Q Gao, B M Martin, M Song, J Cano, A B Farris, A McDonald, E K Gall, C R Dove, F V Leopardi, T How, K D Williams, G R Devi, B H Collins, A D Kirk
Porcine islet xenografts have the potential to provide an inexhaustible source of islets for β cell replacement. Proof-of-concept has been established in nonhuman primates. However, significant barriers to xenoislet transplantation remain, including, the poorly understood instant blood mediated inflammatory reaction (IBMIR), and a thorough understanding of early xeno-specific immune responses. A paucity of data exist comparing xeno-specific immune responses to allo-islet responses in primates. We recently developed a dual islet transplant model, which enables direct histological comparison of early engraftment immunobiology...
November 25, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29160954/islet-allo-autotransplantation-allogeneic-pancreas-transplantation-followed-by-transplant-pancreatectomy-and-islet-transplantation
#18
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/29159905/autologous-mesenchymal-stem-cell-and-islet-cotransplantation-safety-and-efficacy
#19
Hongjun Wang, Charlie Strange, Paul J Nietert, Jingjing Wang, Taylor L Turnbull, Colleen Cloud, Stefanie Owczarski, Betsy Shuford, Tara Duke, Gary Gilkeson, Louis Luttrell, Kathie Hermayer, Jyotika Fernandes, David B Adams, Katherine A Morgan
Islet engraftment after transplantation is impaired by high rates of islet/β cell death caused by cellular stressors and poor graft vascularization. We studied whether cotransplantation of ex vivo expanded autologous bone marrow-derived mesenchymal stem cells (MSCs) with islets is safe and beneficial in chronic pancreatitis patients undergoing total pancreatectomy with islet autotransplantation. MSCs were harvested from the bone marrow of three islet autotransplantation patients and expanded at our current Good Manufacturing Practices (cGMP) facility...
November 21, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29159187/the-role-of-costimulation-blockade-in-solid-organ-and-islet-xenotransplantation
#20
REVIEW
Kannan P Samy, James R Butler, Ping Li, David K C Cooper, Burcin Ekser
Pig-to-human xenotransplantation offers a potential bridge to the growing disparity between patients with end-stage organ failure and graft availability. Early studies attempting to overcome cross-species barriers demonstrated robust humoral immune responses to discordant xenoantigens. Recent advances have led to highly efficient and targeted genomic editing, drastically altering the playing field towards rapid production of less immunogenic porcine tissues and even the discussion of human xenotransplantation trials...
2017: Journal of Immunology Research
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