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https://www.readbyqxmd.com/read/29135052/enhanced-effect-of-human-mesenchymal-stem-cells-expressing-human-tnf-%C3%AE-r-fc-and-ho-1-gene-on-porcine-islet-xenotransplantation-in-humanized-mice
#1
Han-Sin Lee, Sanghyun Song, Du Yeon Shin, Geun-Soo Kim, Jong-Hyun Lee, Chan Woo Cho, Kyo Won Lee, Hyojun Park, Curie Ahn, Jaeseok Yang, Heung-Mo Yang, Jae Berm Park, Sung-Joo Kim
BACKGROUND: Porcine islet xenotransplantation is considered an attractive alternative treatment for type 1 diabetes mellitus. However, it is largely limited because of initial rejection due to Instant Blood-Mediated Inflammatory Reaction (IBMIR), oxidative stress, and inflammatory responses. Recently, soluble tumor necrosis factor-ɑ receptor type I (sTNF-αR) and heme oxygenase (HO)-1 genes (HO-1/sTNF-αR) have been shown to improve the viability and functionality of porcine islets after transplantation...
November 14, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29131417/culturing-with-modified-egm2-medium-enhances-porcine-neonatal-islet-like-cell-clusters-resistance-to-apoptosis-in-islet-xenotransplantation
#2
Xiaoqian Ma, Cejun Yang, Juan Zhang, Jia Wang, Wei Li, Chang Xu, Pengfei Rong, Bin Ye, Minghua Wu, Jianhui Jiang, Shounan Yi, Wei Wang
BACKGROUND: Neonatal pig islet-like cell clusters (NICC) are an attractive source of insulin-producing tissue for potential transplantation treatment of type 1 diabetic patients. However, a considerable loss of NICC after their transplantation due to apoptosis resulted from islet isolation and instant blood-mediated inflammatory reaction remains to be overcome. METHODS: EGM2 medium depleted with hydrocortisone and supplemented with 50 mmol/L isobutylmethylxanthine, 10 mmol/L nicotinamide, and 10 mmol/L glucose was used to culture NICC at day 1, the day after isolation and changed every other day...
November 12, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29099648/a-proteome-analysis-of-pig-pancreatic-islets-and-exocrine-tissue-by-liquid-chromatography-with-tandem-mass-spectrometry
#3
Yoshiki Nakashima, Chika Miyagi-Shiohira, Naoya Kobayashi, Issei Saitoh, Masami Watanabe, Hirofumi Noguchi
Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is a proteome analysis method, and the shotgun analysis by LC-MS/MS comprehensively identifies proteins from tissues and cells with high resolving power. In this study, we analyzed the protein expression in pancreatic tissue by LC-MS/MS. Islets isolated from porcine pancreata (purity ≥95%) and exocrine tissue (purity ≥99%) were used in this study. LC-MS/MS showed that 13 proteins were expressed in pancreatic islets only (Group I), 43 proteins were expressed in both islets and exocrine tissue (Group I&E), and 102 proteins were expressed in exocrine tissue only (Group E)...
November 3, 2017: Islets
https://www.readbyqxmd.com/read/29078330/favorable-outcome-of-experimental-islet-xenotransplantation-without-immunosuppression-in-a-nonhuman-primate-model-of-diabetes
#4
Barbara Ludwig, Stefan Ludwig, Anja Steffen, Yvonne Knauf, Baruch Zimerman, Sophie Heinke, Susann Lehmann, Undine Schubert, Janine Schmid, Martina Bleyer, Uwe Schönmann, Clark K Colton, Ezio Bonifacio, Michele Solimena, Andreas Reichel, Andrew V Schally, Avi Rotem, Uriel Barkai, Helena Grinberg-Rashi, Franz-Josef Kaup, Yuval Avni, Peter Jones, Stefan R Bornstein
Transplantation of pancreatic islets for treating type 1 diabetes is restricted to patients with critical metabolic lability resulting from the need for immunosuppression and the shortage of donor organs. To overcome these barriers, we developed a strategy to macroencapsulate islets from different sources that allow their survival and function without immunosuppression. Here we report successful and safe transplantation of porcine islets with a bioartificial pancreas device in diabetic primates without any immune suppression...
October 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29057561/pre-clinical-results-in-pig-to-non-human-primate-islet-xenotransplantation-using-anti-cd40-antibody-2c10r4-based-immunosuppression
#5
Jun-Seop Shin, Jong-Min Kim, Byoung-Hoon Min, Il Hee Yoon, Hyun Je Kim, Jung-Sik Kim, Yong-Hee Kim, Seong-Jun Kang, Jiyeon Kim, Hee-Jung Kang, Dong-Gyun Lim, Eung-Soo Hwang, Jongwon Ha, Sang-Joon Kim, Wan Beom Park, Chung-Gyu Park
BACKGROUND: Islet transplantation is an effective therapy for selected patients with type 1 diabetes with labile glycemic control and hypoglycemic unawareness, but donor organs are limited. Islet xenotransplantation using porcine islets will potentially solve this problem. Although successful proof of concept studies using clinically inapplicable anti-CD154 monoclonal antibody (mAb) in pig-to-non-human primate (NHP) islet xenotransplantation has been demonstrated by several groups worldwide, potentially clinically applicable anti-CD40 (2C10R4) mAb-based studies have not been reported...
October 22, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28963731/ex-vivo-expanded-baboon-cd39%C3%A2-%C3%A2-regulatory-t-cells-prevent-rejection-of-porcine-islet-xenografts-in-nod-scid-il-2r%C3%AE-mice-reconstituted-with-baboon-peripheral-blood-mononuclear-cells
#6
Dandan Huang, Ya Wang, Wayne J Hawthorne, Min Hu, Joanne Hawkes, Heather Burns, Sussan Davies, Feng Gao, Yi Vee Chew, Shounan Yi, Philip J O'Connell
BACKGROUND: A high immunosuppressive burden is required for long-term islet xenograft survival in non-human primates even using genetically modified donor pigs. AIMS: We aimed to investigate the capacity of baboon regulatory T cells (Treg) to suppress islet xenograft rejection, thereby developing a potential immunoregulatory or tolerance therapy that could be evaluated in NHP models of xenotransplantation. MATERIALS & METHODS: Baboon Treg expanded with stimulation by porcine peripheral blood mononuclear cells (PBMC) were characterized by cell phenotyping and suppressive activity assays in vitro...
September 30, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28937406/tolerance-in-xenotransplantation
#7
Kazuhiko Yamada, Megan Sykes, David H Sachs
PURPOSE OF REVIEW: This review describes recent progress in tolerance-inducing strategies across xenogeneic immunological barriers as well as the potential benefit of a tolerance strategy for islets and kidney xenotransplantation. RECENT FINDINGS: Using advanced gene editing technologies, xenotransplantation from multitransgenic alpha-1,3-galactosyltransferase knockout pigs has demonstrated marked prolongation of renal xenograft survival, ranging from days to greater than several months for life-supporting kidneys, and more than 2 years in a heterotopic nonlife-supporting cardiac xenograft model...
December 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28933628/effectiveness-of-different-molecular-forms-of-c-histolyticum-class-i-collagenase-to-recover-islets
#8
Michael L Green, Andrew G Breite, Caleb A Beechler, Francis E Dwulet, Robert C McCarthy
One factor that may contribute to variability between different lots of purified collagenase to recover islets is the molecular form of C. histolyticum class I (C1) collagenase used in the isolation procedure. Two different enzyme mixtures containing C1, class II (C2) collagenase and BP Protease were compared for their effectiveness to recover islets from split adult porcine pancreas. The same enzyme activities per g trimmed tissue were used for all isolations with the only difference being the mass of C1 required to achieve 25,000 collagen degradation activity U/g tissue...
September 21, 2017: Islets
https://www.readbyqxmd.com/read/28932650/gene-editing-gene-therapy-and-cell-xenotransplantation-cell-transplantation-across-species
#9
REVIEW
Nizar I Mourad, Pierre Gianello
PURPOSE OF REVIEW: Cell xenotransplantation has the potential to provide a safe, ethically acceptable, unlimited source for cell replacement therapies. This review focuses on genetic modification strategies aimed to overcome remaining hurdles standing in the way of clinical porcine islet transplantation and to develop neural cell xenotransplantation. RECENT FINDINGS: In addition to previously described genetic modifications aimed to mitigate hyperacute rejection, instant blood-mediated inflammatory reaction, and cell-mediated rejection, new data showing the possibility of increasing porcine islet insulin secretion by transgenesis is an interesting addition to the array of genetically modified pigs available for xenotransplantation...
2017: Current Transplantation Reports
https://www.readbyqxmd.com/read/28931557/protective-effect-of-cyanidin-3-o-glucoside-on-neonatal-porcine-islets
#10
Chao Li, Bin Yang, Zhihao Xu, Eric Boivin, Mazzen Black, Wenlong Huang, Baoyou Xu, Ping Wu, Bo Zhang, Xian Li, Kunsong Chen, Yulian Wu, Gina R Rayat
Oxidative stress is a major cause of islet injury and dysfunction during isolation and transplantation procedures. Cyanidin-3-O-glucoside (C3G), which is present in various fruits and vegetables especially in Chinese bayberry, shows a potent antioxidant property. In this study, we determined whether C3G could protect neonatal porcine islets (NPI) from reactive oxygen species (H2O2)-induced injury in vitro and promote the function of NPI in diabetic mice. We found that C3G had no deleterious effect on NPI and that C3G protected NPI from damage induced by H2O2 Significantly higher hemeoxygenase-1 (HO1) gene expression was detected in C3G-treated NPI compared to untreated islets before and after transplantation (P < 0...
December 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28915137/xenoislets-porcine-pancreatic-islets-for-the-treatment-of-type-i-diabetes
#11
Nizar I Mourad, Pierre Rene Gianello
PURPOSE OF REVIEW: Porcine islets are being extensively investigated as alternative sources of insulin-secreting cells for transplantation in insulin-dependent diabetic patients. The present review focuses on recent advances in porcine islet transplantation with particular emphasis on new transgenic pig models, islet encapsulation, and biosafety considerations. RECENT FINDINGS: Genetic modifications aimed to reduce islet cell immunogenicity, to prolong their survival, and to improve their secretory function have been reported...
December 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28905065/be-positive-optimizing-pramlintide-from-microcanonical-analysis-of-amylin-isoforms
#12
Rafael B Frigori
Amylin, or human islet amyloid polypeptide (hIAPP), is a 37-residue hormone synergistic to insulin and co-secreted with it by β-cells in the pancreas. The deposition of its cytotoxic amyloid fibrils is strongly related to the progression of Type II diabetes (T2D) and islet graft failures. Notably, isoforms from some mammalian species, such as rats (rIAPP) and porcine (pIAPP), present a few key mutations preventing aggregation. This has lead to biotechnological development of drugs for adjunct therapies of T2D, such as pramlintide, a variant of hIAPP inspired by rIAPP whose proline substitutions have β-strand fibril-breaking properties...
September 27, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28759462/pig-islet-xenotransplantation
#13
Maheswaran Dhanasekaran, Johnathan J George, Gopalakrishnan Loganathan, Siddharth Narayanan, Michael G Hughes, Stuart K Williams, Appakalai N Balamurugan
PURPOSE OF REVIEW: The current article reviews the rationale, sources and preparation of pig islets for xenotransplantation, and presents current progress in solving the problems associated with establishing pig islet transplant as a clinical treatment for type 1 diabetes. SUMMARY: Islet transplantation is an effective treatment option for type 1 diabetes, but the available supply of human pancreases is insufficient to meet the need and demand for obtaining islets...
July 28, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28748550/porcine-c-peptide-measurement-to-assess-graft-function-in-xenogeneic-porcine-islet-transplantation-editorial-commentary
#14
Henk-Jan Schuurman
No abstract text is available yet for this article.
July 26, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28731212/cross-validation-of-commercial-enzyme-linked-immunosorbent-assay-and-radioimmunoassay-for-porcine-c-peptide-concentration-measurements-in-non-human-primate-serum
#15
Sarah C Gresch, Lucas A Mutch, Jody L Janecek, Rebecca L Hegstad-Davies, Melanie L Graham
BACKGROUND: C-peptide concentration is widely used as a marker of insulin secretion and is especially relevant in evaluating islet graft function following transplantation, because its measurement is not confounded by the presence of exogenous insulin. To address the shortage of human islet donors, the use of porcine islets has been proposed as a possible solution and the stringent pig-to-non-human primate (NHP) model is often the most relevant for pre-clinical evaluation of the potential for diabetes reversal resulting from an islet xenograft...
July 21, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28730558/transplantation-sites-for-porcine-islets
#16
Rebecca A Stokes, Denbigh M Simond, Heather Burns, Anita T Patel, Philip J O'Connell, Jenny E Gunton, Wayne J Hawthorne
AIMS/HYPOTHESIS: Xenotransplantation has great potential to provide beta cell replacement and thereby provide a cure for large numbers of people with type 1 diabetes. Crucial to the success of xenotransplantation is establishment of the most viable sites for transplantation. METHODS: We compared porcine islet tissue transplanted into kidney, liver and spleen in pig recipients as assessed by blood glucose levels and IVGTT. RESULTS: Kidney was the superior site for porcine islet tissue transplantation, followed by liver then spleen...
October 2017: Diabetologia
https://www.readbyqxmd.com/read/28623861/level-of-acceptance-of-islet-cell-and-kidney-xenotransplants-by-personnel-of-hospitals-with-and-without-experience-in-clinical-xenotransplantation
#17
Adrian Abalovich, Shinichi Matsumoto, Carlos J Wechsler, Mariana E Carulla, Martín E Siciliano, Daniel Sznaider, Joachim Denner, Robert B Elliott
BACKGROUND: Recently, significant progress in both safety and efficacy has been achieved in the field of xenotransplantation, as exemplified by results from the first clinical trials of porcine islet transplantation. It would be of interest to learn whether the attitude of the clinical staff involved in such trials changes as the trials are carried out in their own hospital. METHODS: One hundred and four clinical staff members from the Eva Peron Hospital of San Martin (Buenos Aires, Argentina) where clinical trials of islet xenotransplantation have been performed and 92 similar staff members from the Diego Thompson Hospital (Buenos Aires, Argentina) where no such xenotransplantation has been carried out participated in the study...
July 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28620237/lea29y-expression-in-transgenic-neonatal-porcine-islet-like-cluster-promotes-long-lasting-xenograft-survival-in-humanized-mice-without-immunosuppressive-therapy
#18
L Wolf-van Buerck, M Schuster, F S Oduncu, A Baehr, T Mayr, S Guethoff, J Abicht, B Reichart, N Klymiuk, E Wolf, J Seissler
Genetically engineered pigs are a promising source for islet cell transplantation in type 1 diabetes, but the strong human anti-pig immune response prevents its successful clinical application. Here we studied the efficacy of neonatal porcine islet-like cell clusters (NPICCs) overexpressing LEA29Y, a high-affinity variant of the T cell co-stimulation inhibitor CTLA-4Ig, to engraft and restore normoglycemia after transplantation into streptozotocin-diabetic NOD-SCID IL2rγ(-/-) (NSG) mice stably reconstituted with a human immune system...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28616498/xenotransplantation-a-special-case-of-one-health
#19
REVIEW
Joachim Denner
The chronic shortage of human transplants to treat tissue and organ failure has led to the development of xenotransplantation, the transplantation of cells, tissues and organs from another species to human recipients. For a number of reasons, pigs are best suited as donor animals. Successful, routine xenotransplantation would have an enormous impact on the health of the human population, including the young, who sometimes require a replacement organ or islet cells, but especially the elderly, who more often suffer the consequences of organ failure...
June 2017: One Health
https://www.readbyqxmd.com/read/28554010/a-bilaminated-decellularized-scaffold-for-islet-transplantation-structure-properties-and-functions-in-diabetic-mice
#20
Xi Wang, Kai Wang, Wei Zhang, Ming Qiang, Ying Luo
Ectopic transplantation of islets provides a beta cell-replacement approach that may allow the recovery of physiological regulation of the blood sugar level in patients with Type I diabetes (T1D). In development of new extrahepatic islet transplantation protocols in support of the islet engraftment, it is pivotal to develop scaffold materials with multifaceted functions to provide beneficial microenvironment, mediate host response in favor of vascularization/islet integration and maintain long-term islet function at the transplantation site...
May 22, 2017: Biomaterials
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