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Pancreas cells transplantation

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https://www.readbyqxmd.com/read/29781950/report-of-the-key-opinion-leaders-meeting-on-stem-cell-derived-beta-cells
#1
Jon Odorico, James Markmann, Douglas Melton, Julia Greenstein, Albert Hwa, Cristina Nostro, Alireza Rezania, Jose Oberholzer, Daniel Pipeleers, Luhan Yang, Chad Cowan, Danwei Huangfu, Dieter Egli, Uri Ben-David, Ludovic Vallier, Shane T Grey, Qizhi Tang, Bart Roep, Camilo Ricordi, Ali Naji, Giuseppe Orlando, Daniel G Anderson, Mark Poznansky, Barbara Ludwig, Alice Tomei, Dale L Greiner, Melanie Graham, Melissa Carpenter, Giovanni Migliaccio, Kevin D'Amour, Bernhard Hering, Lorenzo Piemonti, Thierry Berney, Mike Rickels, Thomas Kay, Ann Adams
Beta cell replacement has the potential to restore euglycemia in patients with insulin dependent diabetes. While great progress has been made in establishing allogeneic islet transplantation from deceased donors as the standard of care for those with the most labile diabetes, it is also clear that the deceased donor organ supply cannot possibly treat all those who could benefit from restoration of a normal beta cell mass, especially if immunosuppression were not required. Against this background, the International Pancreas and Islet Transplant Association (IPITA) in collaboration with the Harvard Stem Cell Institute (HSCI), the Juvenile Diabetes Research Foundation (JDRF), and the Helmsley Foundation held a 2-day Key Opinion Leaders Meeting in Boston in 2016 to bring together experts in generating and transplanting beta cells derived from stem cells...
April 30, 2018: Transplantation
https://www.readbyqxmd.com/read/29769672/pancreas-regeneration
#2
REVIEW
Qiao Zhou, Douglas A Melton
The pancreas is made from two distinct components: the exocrine pancreas, a reservoir of digestive enzymes, and the endocrine islets, the source of the vital metabolic hormone insulin. Human islets possess limited regenerative ability; loss of islet β-cells in diseases such as type 1 diabetes requires therapeutic intervention. The leading strategy for restoration of β-cell mass is through the generation and transplantation of new β-cells derived from human pluripotent stem cells. Other approaches include stimulating endogenous β-cell proliferation, reprogramming non-β-cells to β-like cells, and harvesting islets from genetically engineered animals...
May 2018: Nature
https://www.readbyqxmd.com/read/29768476/treatment-with-specific-soluble-factors-promotes-the-functional-maturation-of-transcription-factor-mediated-pancreatic-transdifferentiated-cells
#3
Hiroaki Motoyama, Akira Kobayashi, Takahide Yokoyama, Akira Shimizu, Hiroshi Sakai, Tsuyoshi Notake, Kentaro Fukushima, Shin-Ichi Miyagawa
Pancreatic lineage-specific transcription factors (TFs) display instructive roles in converting adult cells to endocrine pancreatic cells through a process known as transdifferentiation. However, little is known about potential factors capable of accelerating transdifferentiation following transduction to achieve the functional maturation of transdifferentiated cells. In this study, we demonstrated, using adult liver-derived progenitor cells, that soluble factors utilized in pancreatic differentiation protocols of pluripotent stem cells promote functional maturation of TFs-mediated transdifferentiated cells...
2018: PloS One
https://www.readbyqxmd.com/read/29757902/differential-impact-of-t-bet-and-ifn%C3%AE-on-pancreatic-islet-allograft-rejection
#4
Alix Besançon, Zeynep Demir, Tania Goncalves, Fabrice Valette, Emilie Panafieu, Lucienne Chatenoud, Sylvaine You
BACKGROUND: T-cell-mediated graft rejection is mostly correlated with potent Th1 responses. However, since IFNγ mice reject their graft as efficiently as wild-type (WT) mice, the exact contribution of IFNγ and its transcription factor T-bet remains a matter of debate. Here, we address this question in the context of pancreatic islet allograft to better inform the molecular pathways that hampers islet survival in vivo. METHODS: Pancreatic islets from BALB/c mice were transplanted in WT, IFNγ or T-bet C57BL/6 mice...
May 2, 2018: Transplantation
https://www.readbyqxmd.com/read/29723228/divergent-antioxidant-capacity-of-human-islet-cell-subsets-a-potential-cause-of-beta-cell-vulnerability-in-diabetes-and-islet-transplantation
#5
Atsushi Miki, Camillo Ricordi, Yasunaru Sakuma, Toshiyuki Yamamoto, Ryosuke Misawa, Atsuyoshi Mita, Ruth D Molano, Nosratola D Vaziri, Antonello Pileggi, Hirohito Ichii
BACKGROUND: Type 1 and Type 2 diabetes mellitus (T1DM and T2DM) are caused by beta(β)-cell loss and functional impairment. Identification of mechanisms of β-cell death and therapeutic interventions to enhance β-cell survival are essential for prevention and treatment of diabetes. Oxidative stress is a common feature of both T1DM and T2DM; elevated biomarkers of oxidative stress are detected in blood, urine and tissues including pancreas of patients with DM. Islet transplantation is a promising treatment for diabetes...
2018: PloS One
https://www.readbyqxmd.com/read/29717931/-re-generating-human-beta-cells-status-pitfalls-and-perspectives
#6
Luc Baeyens, Marie Lemper, Willem Staels, Sofie De Groef, Nico De Leu, Yves Heremans, Michael S German, Harry Heimberg
Diabetes mellitus results from disturbed glucose homeostasis due to an absolute (type 1) or relative (type 2) deficiency of insulin, a peptide hormone almost exclusively produced by the beta cells of the endocrine pancreas in a tightly regulated manner. Current therapy only delays disease progression through insulin injection and/or oral medications that increase insulin secretion or sensitivity, decrease hepatic glucose production, or promote glucosuria. These drugs have turned diabetes into a chronic disease as they do not solve the underlying beta cell defects or entirely prevent the long-term complications of hyperglycemia...
July 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29691708/generation-of-insulin-deficient-piglets-by-disrupting-ins-gene-using-crispr-cas9-system
#7
Bumrae Cho, Su Jin Kim, Eun-Jin Lee, Sun Mi Ahn, Jin Seok Lee, Dal-Young Ji, Kiho Lee, Jung-Taek Kang
Diabetes mellitus is a chronic disease with accompanying severe complications. Various animal models, mostly rodents due to availability of genetically modified lines, have been used to investigate the pathophysiology of diabetes. Using pigs for diabetic research can be beneficial because of their similarity in size, pathogenesis pathway, physiology, and metabolism with human. However, the use of pigs for diabetes research has been hampered due to only few pig models presenting diabetes symptoms. In this study, we have successfully generated insulin-deficient pigs by generating the indels of the porcine INS gene in somatic cells using CRISPR/Cas9 system followed by somatic cell nuclear transfer...
April 24, 2018: Transgenic Research
https://www.readbyqxmd.com/read/29675567/human-urine-derived-stem-cells-play-a-novel-role-in-the-treatment-of-stz-induced-diabetic-mice
#8
Tianxue Zhao, Deng Luo, Yun Sun, Xin Niu, Yang Wang, Chen Wang, Weiping Jia
Human urine-derived stem cells (hUSCs) are a potential stem cell source for cell therapy. However, the effect of hUSCs on glucose metabolism regulation in type 1 diabetes was not clear. Therefore, the aim of the study was to evaluate whether hUSCs have protective effect on streptozotocin (STZ)-induced diabetes. hUSCs were extracted and cultivated with a special culture medium. Flow cytometry analysis was applied to detect cell surface markers. BALB/c male nude mice were either injected with high-dose STZ (HD-STZ) or multiple low-dose STZ (MLD-STZ)...
April 19, 2018: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29622345/early-islets-and-mesenchyme-from-an-injured-adult-pancreas-improve-syngeneic-engraftments-and-islet-graft-function-in-diabetic-rats
#9
Venant Tchokonte-Nana, Juziel Kampando Manda
A decrease in mass of isografts and a decline in islet function are major challenges in islet transplantations. Despite this, transplantation of 84 h harvested pancreatic duct ligation (PDL) tissues have been shown to have the same functional ability to foetal pancreata, but there was only 40% success in reverting hyperglycaemia. We tested the potential of early islets with mesenchymal stromal cells (MSCs) to promote isogeneic grafts survival and to restore normoglycemia in diabetic rats, in comparison with late islets...
April 2, 2018: Acta Histochemica
https://www.readbyqxmd.com/read/29620617/pancreas-transplantation-from-pediatric-donors-a-single-center-experience
#10
Mario Spaggiari, Caterina Di Bella, Pierpaolo Di Cocco, Maya Campara, Kelly Galen, Federico Gheza, Jose Oberholzer, Enrico Benedetti, Ivo Tzvetanov
BACKGROUND: Pancreas allografts from pediatric donors are considered less suitable due to the increased risk of surgical complications and reduced islet cell mass that may compromise function. METHODS: All pancreatic transplants, procured from donors <18 years old, between January 2007 and March 2017, were included in the analysis. The grafts were subdivided into 3 groups by donor's weight: <30kg, 30-60kg, >60kg. Analysis of patient and graft survival was done between the groups, and subsequently between the pediatric cohort and the adult-donor control group...
April 3, 2018: Transplantation
https://www.readbyqxmd.com/read/29617192/optical-clearing-of-the-pancreas-for-visualization-of-mature-%C3%AE-cells-and-vessels-in-mice
#11
Wataru Nishimura, Asako Sakaue-Sawano, Satoru Takahashi, Atsushi Miyawaki, Kazuki Yasuda, Yasuko Noda
Glucose metabolism is regulated by insulin, which is produced from β-cells in the pancreas. Because insulin is secreted into vessels in response to blood glucose, vascular structures of the pancreas, especially the relationship between vessels and β-cells, are important for physiological and pathological glucose metabolism. Here, we developed a system to visualize vessels surrounding mature β-cells expressing transcription factor MafA in a three-dimensional manner. Optical clearing of the pancreas prevented light scattering of fluorescence driven by the bacterial artificial chromosome (BAC)-mafA promoter in β-cells...
April 4, 2018: Islets
https://www.readbyqxmd.com/read/29611212/design-of-bioartificial-pancreases-from-the-standpoint-of-oxygen-supply
#12
Hiroo Iwata, Yusuke Arima, Yusuke Tsutsui
A bioartificial pancreas (BAP), in which islets of Langerhans (islets) are enclosed in a semipermeable membrane, has been developed to realize islet transplantation without the use of immunosuppressive drugs. Although recent progress in induced pluripotent stem (iPS) and embryonic stem (ES) cells has attracted attention owing to the potential applications of these cells as insulin-releasing cells, concerns about the safety of implantation of these cells remain. The use of the BAP has the advantage of easy removal if insulin-releasing cells derived from iPS/ES cells undesirably proliferate and form tumors in the BAP...
April 2, 2018: Artificial Organs
https://www.readbyqxmd.com/read/29606260/-transplantation-strategy-in-type-1-diabetic-patients
#13
Fanny Buron, Lionel Badet, Emmanuel Morelon
Beta cell replacement by pancreas or Langerhans islets transplantation is the only way to restore glucose homeostasis in type 1 diabetic patients. The counterpart is the need for long-term immunosuppression. These transplantations are therefore mainly indicated for patients candidates for kidney transplantation and for patients with poor quality of life due to unstable diabetes with life-threatening hypoglycemic events. Both beta cell replacement techniques have different benefits and risks and should be adapted to each type 1 diabetic patient...
April 2018: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/29599935/bk-virus-associated-collecting-duct-carcinoma-of-the-renal-allograft-in-a-kidney-pancreas-allograft-recipient
#14
Myriam Dao, Adrien Pécriaux, Thomas Bessede, Antoine Dürrbach, Charlotte Mussini, Catherine Guettier, Sophie Ferlicot
BK polyomavirus (BKV) nephropathy is a major concern in renal transplantation. Its main consequence is graft loss, which occurs in more than 50% of the cases. De novo renal cell carcinoma in renal allograft is a very rare event. Most of these tumors are papillary or clear cell carcinomas. We report herein the first case of collecting duct carcinoma of the renal allograft in a kidney-pancreas allograft adult recipient. Collecting duct carcinoma occurs long after the cure of a BKV nephropathy. At this time, BKV viremia and viruria were negative as well as the immunostaining for SV40 in the non-tumor kidney...
March 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29599125/establishment-of-human-pluripotent-stem-cell-derived-pancreatic-%C3%AE-like-cells-in-the-mouse-pancreas
#15
Haiting Ma, Katherine J Wert, Dmitry Shvartsman, Douglas A Melton, Rudolf Jaenisch
Type 1 diabetes is characterized by autoimmune destruction of β cells located in pancreatic islets. However, tractable in vivo models of human pancreatic β cells have been limited. Here, we generated xenogeneic human pancreatic β-like cells in the mouse pancreas by orthotopic transplantation of stem cell-derived β (SC-β) cells into the pancreas of neonatal mice. The engrafted β-like cells expressed β cell transcription factors and markers associated with functional maturity. Engrafted human cells recruited mouse endothelial cells, suggesting functional integration...
March 29, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29597032/current-advanced-therapy-cell-based-medicinal-products-for-type-1-diabetes-treatment
#16
REVIEW
Alberto Cañibano-Hernández, Laura Sáenz Del Burgo, Albert Espona-Noguera, Jesús Ciriza, Jose Luis Pedraz
In the XXI century diabetes mellitus has become one of the main threats to human health with higher incidence in regions such as Europe and North America. Type 1 diabetes mellitus (T1DM) occurs as a consequence of the immune-mediated destruction of insulin producing β-cells located in the endocrine part of the pancreas, the islets of Langerhans. The administration of exogenous insulin through daily injections is the most prominent treatment for T1DM but its administration is frequently associated to failure in glucose metabolism control, finally leading to hyperglycemia episodes...
March 27, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29593968/engineering-a-tumor-microenvironment-mimetic-niche-for-tissue-regeneration-with-xenogeneic-cancer-cells
#17
Zhenzhen Wang, Chunming Wang, Ayipaxia Abudukeremu, Xiaying Rui, Shang Liu, Xiaoyi Zhang, Min Zhang, Junfeng Zhang, Lei Dong
The insufficient number of cells suitable for transplantation is a long-standing problem to cell-based therapies aimed at tissue regeneration. Xenogeneic cancer cells (XCC) may be an alternative source of therapeutic cells, but their transplantation risks both immune rejection and unwanted spreading. In this study, a strategy to facilitate XCC transplantation is reported and their spreading in vivo is confined by constructing an engineering matrix that mimics the characteristics of tumor microenvironment. The data show that this matrix, a tumor homogenate-containing hydrogel (THAG), successfully creates an immunosuppressive enclave after transplantation into immunocompetent mice...
March 2018: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/29579886/pancreas-donor-hypernatremia-is-it-really-a-risk-factor-for-simultaneous-pancreas-kidney-transplantation
#18
J M Sánchez-Hidalgo, L Rodríguez-Ortiz, A Arjona-Sánchez, J Ruiz-Rabelo, J J Salamanca-Bustos, A Rodríguez-Benot, F J Márquez-López, J Briceño-Delgado
INTRODUCTION: Solid organ donor hypernatremia has been classically reported to be a risk factor for cell lysis and graft damage. National criteria for pancreatic donation consider severe hypernatremia (sodium level more than 160 mEq/L) to be relative exclusion criteria. The aim of our study is to review the postoperative outcomes of our simultaneous pancreas-kidney transplantation (SPKT) sample in terms of pancreatic fistula, intra-abdominal abscesses, pancreatitis, pancreas graft thrombosis, early pancreatectomy, and reoperation rates regarding different ranges of donor sodium levels...
March 2018: Transplantation Proceedings
https://www.readbyqxmd.com/read/29565508/islet-transplantation-30-years-after-the-first-transplants
#19
B Antonioli, M Galuzzi
First clinical islet allotransplantation in patients affected by type 1 diabetes mellitus was performed about 30 years ago. Despite the progressive improvement of the success rate, the clinical indication to the islet allotransplantation remains limited to selected patients affected by brittle type 1 diabetes mellitus. The burden of the immunosuppression therapy still represents the main critical issue but other areas might be subject to further improvements, such as the islet production, islet engraftment and long-term function...
March 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29546813/endothelial-and-beta-cell-composite-aggregates-for-improved-function-of-a-bioartificial-pancreas-encapsulation-device
#20
Katarzyna Skrzypek, Yazmin Brito Barrera, Thomas Groth, Dimitrios Stamatialis
INTRODUCTION: Encapsulation of pancreatic islets or beta cells is a promising strategy for treatment of type 1 diabetes by providing an immune isolated environment and allowing for transplantation in a different location than the liver. However, islets used for encapsulation often show lower functionality due to the damaging of islet endothelial cells during the isolation procedure. Factors produced by endothelial cells have great impact on beta cell insulin secretion. Therefore, mutual signaling between endothelial cells and beta cells should be considered for the development of encapsulation systems to achieve high insulin secretion and maintain beta cell viability...
March 2018: International Journal of Artificial Organs
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