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Pig islets

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https://www.readbyqxmd.com/read/29782054/assessment-of-porcine-endogenous-retrovirus-transmission-across-an-alginate-barrier-used-for-the-encapsulation-of-porcine-islets
#1
Claire Crossan, Nizar I Mourad, Karen Smith, Pierre Gianello, Linda Scobie
BACKGROUND: Subcutaneous implantation of a macroencapsulated patch containing human allogenic islets has been successfully used to alleviate type 1 diabetes mellitus (T1DM) in a human recipient without the need for immunosuppression. The use of encapsulated porcine islets to treat T1DM has also been reported. Although no evidence of pathogen transfer using this technology has been reported to date, we deemed it appropriate to determine if the encapsulation technology would prevent the release of virus, in particular, the porcine endogenous retrovirus (PERV)...
May 21, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29693599/dietary-supplementation-with-oleum-cinnamomi-improves-intestinal-functions-in-piglets
#2
Dan Yi, Qiuhong Fang, Yongqing Hou, Lei Wang, Haiwang Xu, Tao Wu, Joshua Gong, Guoyao Wu
The present study was to determine the efficacy of dietary supplementation with oleum cinnamomi (OCM) on growth performance and intestinal functions in piglets. Sixteen piglets (24-day-old) were randomly assigned to the control or OCM groups. Piglets in the control group were fed a basal diet, whereas piglets in the OCM group were fed the basal diet supplemented with 50 mg/kg OCM. On day 20 of the trial, blood samples and intestinal tissues were obtained from piglets. Compared with the control group, dietary OCM supplementation increased ( p < 0...
April 25, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29691708/generation-of-insulin-deficient-piglets-by-disrupting-ins-gene-using-crispr-cas9-system
#3
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/29602717/skin-xenotransplantation-historical-review-and-clinical-potential
#4
REVIEW
Takayuki Yamamoto, Hayato Iwase, Timothy W King, Hidetaka Hara, David K C Cooper
Half a million patients in the USA alone require treatment for burns annually. Following an extensive burn, it may not be possible to provide sufficient autografts in a single setting. Pig skin xenografts may provide temporary coverage. However, preformed xenoreactive antibodies in the human recipient activate complement, and thus result in rapid rejection of the graft. Because burn patients usually have some degree of immune dysfunction and are therefore at increased risk of infection, immunosuppressive therapy is undesirable...
March 27, 2018: Burns: Journal of the International Society for Burn Injuries
https://www.readbyqxmd.com/read/29601985/mechanical-characterization-and-numerical-simulation-of-a-subcutaneous-implantable-3d-printed-cell-encapsulation-system
#5
Federica Adamo, Marco Farina, Usha R Thekkedath, Alessandro Grattoni, Raffaella Sesana
Cell transplantation in bioengineered scaffolds and encapsulation systems has shown great promise in regenerative medicine. Depending on the site of implantation, type of cells and their expected function, these systems are designed to provide cells with a physiological-like environment while providing mechanical support and promoting long-term viability and function of the graft. A minimally invasive 3D printed system termed neovascularized implantable cell homing and encapsulation (NICHE) was developed in polylactic acid for subcutaneous transplantation of endocrine cells, including pancreatic islets...
March 21, 2018: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/29550793/orexin-a-modulates-endocrine-function-and-viability-of-porcine-pancreatic-islets
#6
M Sassek, E Pruszynska-Oszmalek, K W Nowak
The physiology of porcine pancreatic islets is poorly understood. Orexin A is one of important agents regulating the physiology of porcine pancreatic islets. This study aimed to determine the potential effect of orexin A on the functioning of porcine pancreatic islets. Orexin receptor localization was done by PCR (polymerase chain reaction) and Western Blot, both in pancreatic isolated islets and whole pancreas. Secretion of insulin and glucagon from islets after orexin-A treatment was assayed. The viability of pig pancreatic islet cells and level of cleaved/total caspase 3 protein were measured by MTT test (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Western blotting, respectively...
December 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29517421/development-of-a-polarized-pancreatic-ductular-cell-epithelia-for-physiological-studies
#7
Yunxia O'Malley, Pavana G Rotti, Ian M Thornell, Oriana G Vanegas Calderón, Christopher Febres-Aldana, Katelin Durham, Jianrong Yao, Xiaopeng Li, Zheng Zhu, Andrew W Norris, Joseph Zabner, John F Engelhardt, Aliye Uc
Pancreatic ductular epithelial cells comprise the majority of duct cells in pancreas, control cystic fibrosis transmembrane conductance regulator (CFTR)-dependent bicarbonate [HCO3 - ] secretion, but are difficult to grow as a polarized monolayer. Using NIH-3T3-J2 fibroblast feeder cells and a Rho-associated kinase inhibitor, we produced well-differentiated and polarized porcine pancreatic ductular epithelial cells. Cells grown on semipermeable filters at air-liquid interface (ALI) developed typical epithelial cell morphology and stable transepithelial resistance (TER), expressed epithelial cell markers (zona occludens-1 and beta catenin), duct cell markers (SOX-9 and CFTR), but no acinar (amylase) or islet cell (chromogranin) markers...
March 8, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29427659/construction-of-emsc-islet-co-localizing-composites-for-xenogeneic-porcine-islet-transplantation
#8
Jung-Sik Kim, Hyunwoo Chung, Nari Byun, Seong-Jun Kang, Sunho Lee, Jun-Seop Shin, Chung-Gyu Park
Pancreatic islet transplantation is an ultimate solution for treating patients with type 1 diabetes (T1D). The pig is an ideal donor of islets for replacing scarce human islets. Besides immunological hurdles, non-immunological hurdles including fragmentation and delayed engraftment of porcine islets need solutions to succeed in porcine islet xenotransplantation. In this study, we suggest a simple but effective modality, a cell/islet co-localizing composite, to overcome these challenges. Endothelial-like mesenchymal stem cells (EMSCs), differentiated from bone-marrow derived mouse mesenchymal stem cells (MSCs), and MSCs evenly coated the surface of porcine islets (>85%) through optimized culture conditions...
March 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29406755/structural-modulation-of-human-amylin-protofilaments-by-naturally-occurring-mutations
#9
Florentina Tofoleanu, Ye Yuan, Frank C Pickard, Bartłomiej Tywoniuk, Bernard R Brooks, Nicolae-Viorel Buchete
Human islet amyloid polypeptide (hIAPP), also known as amylin, is a 37-amino-acid peptide, co-secreted with insulin, and widely found in fibril form in type-2 diabetes patients. By using all-atom molecular dynamics simulations, we study hIAPP fibril segments (i.e., fibrillar oligomers) formed with sequences of naturally occurring variants from cat, rat, and pig, presenting different aggregation propensities. We characterize the effect of mutations on the structural dynamics of solution-formed hIAPP fibril models built from solid-state NMR data...
February 21, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29359356/the-value-of-glycated-albumin-for-the-prediction-of-graft-outcome-in-the-non-human-primate-porcine-islet-transplantation-model
#10
Hee Jung Kang, Haneulnari Lee, Eun Mi Park, Jong-Min Kim, Jun-Seop Shin, Chung-Gyu Park
BACKGROUND: The development of a precise and easy-to-use tool for monitoring islet graft function is important in clarifying the causes of graft loss, identifying appropriate therapy, and ensuring graft survival in the nonhuman primate (NHP) model of porcine islet transplantation (PITx). Glycated albumin (GA) is an indicator of intermediate-term changes in blood glucose control and is useful in clinical diabetes management. The validity of GA for monitoring graft function in NHP recipients of PITx was evaluated using a retrospective analysis of cohort samples...
March 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29352230/histology-immunohistochemistry-and-in-situ-hybridization-reveal-overlooked-ebola-virus-target-tissues-in-the-ebola-virus-disease-guinea-pig-model
#11
Timothy K Cooper, Louis Huzella, Joshua C Johnson, Oscar Rojas, Sri Yellayi, Mei G Sun, Sina Bavari, Amanda Bonilla, Randy Hart, Peter B Jahrling, Jens H Kuhn, Xiankun Zeng
Survivors of Ebola virus infection may become subclinically infected, but whether animal models recapitulate this complication is unclear. Using histology in combination with immunohistochemistry and in situ hybridization in a retrospective review of a guinea pig confirmation-of-virulence study, we demonstrate for the first time Ebola virus infection in hepatic oval cells, the endocardium and stroma of the atrioventricular valves and chordae tendinae, satellite cells of peripheral ganglia, neurofibroblasts and Schwann cells of peripheral nerves and ganglia, smooth muscle cells of the uterine myometrium and vaginal wall, acini of the parotid salivary glands, thyroid follicular cells, adrenal medullary cells, pancreatic islet cells, endometrial glandular and surface epithelium, and the epithelium of the vagina, penis and, prepuce...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29228112/xenotransplantation-the-current-status-and-prospects
#12
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...
March 1, 2018: British Medical Bulletin
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
#13
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...
January 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29208633/in-vivo-visualization-of-%C3%AE-cells-by-targeting-of-gpr44
#14
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 β-cell selective in the human pancreas and constitutes a tentative surrogate imaging biomarker in diabetes. A radiolabeled small-molecule GPR44 antagonist, [11 C]AZ12204657, was evaluated for visualization of β-cells in pigs and nonhuman primates by positron emission tomography as well as in immunodeficient mice transplanted with human islets under the kidney capsule. In vitro autoradiography of human and animal pancreatic sections from subjects without and with diabetes, in combination with insulin staining, was performed to assess β-cell selectivity of the radiotracer...
February 2018: Diabetes
https://www.readbyqxmd.com/read/29159187/the-role-of-costimulation-blockade-in-solid-organ-and-islet-xenotransplantation
#15
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
https://www.readbyqxmd.com/read/29131417/culturing-with-modified-egm2-medium-enhances-porcine-neonatal-islet-like-cell-clusters-resistance-to-apoptosis-in-islet-xenotransplantation
#16
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...
January 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29131413/the-effect-of-epitope-based-ligation-of-icam-1-on-survival-and-retransplantation-of-pig-islets-in-nonhuman-primates
#17
Jae-Il Lee, Jiyeon Kim, Yun-Jung Choi, Hi-Jung Park, Hye-Jin Park, Hae Joo Wi, Sunok Yoon, Jun-Seop Shin, Jin Kyun Park, Kyeong Cheon Jung, Eun Bong Lee, Hee Jung Kang, Eung Soo Hwang, Sang-Joon Kim, Chung-Gyu Park, Seong Hoe Park
BACKGROUND: Pig islet xenotransplantation is a promising alternative to allogeneic transplantation. However, the wide immunologic barrier between pigs and primates limits the long-term survival of the graft. MD-3, a novel monoclonal antibody (mAb) that recognizes a particular epitope of human ICAM-1, can render T cells tolerant to a xenograft by arresting dendritic cell maturation. We report the long-term survival of adult wild-type pig islets and successful retransplantation in nonhuman primates using a protocol comprising induction with MD-3 mAb and maintenance with anti-CD154 mAb and sirolimus...
January 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29099648/a-proteome-analysis-of-pig-pancreatic-islets-and-exocrine-tissue-by-liquid-chromatography-with-tandem-mass-spectrometry
#18
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 2, 2017: Islets
https://www.readbyqxmd.com/read/29057561/pre-clinical-results-in-pig-to-non-human-primate-islet-xenotransplantation-using-anti-cd40-antibody-2c10r4-based-immunosuppression
#19
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...
January 2018: Xenotransplantation
https://www.readbyqxmd.com/read/28984038/beta-cell-replacement-strategies-for-diabetes
#20
REVIEW
Timothy J Kieffer, Knut Woltjen, Kenji Osafune, Daisuke Yabe, Nobuya Inagaki
Diabetes is characterized by elevated levels of blood glucose as a result of insufficient production of insulin from loss or dysfunction of pancreatic islet β-cells. Here, we review several approaches to replacing β-cells that were recently discussed at a symposium held in Kyoto, Japan. Transplant of donor human islets can effectively treat diabetes and eliminate the need for insulin injections, supporting research aimed at identifying abundant supplies of cells. Studies showing the feasibility of producing mouse islets in rats support the concept of generating pigs with human pancreas that can serve as donors of human islets, although scientific and ethical challenges remain...
October 6, 2017: Journal of Diabetes Investigation
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