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Xenotransplantation

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https://www.readbyqxmd.com/read/28437635/three-cysteine-residues-of-slc52a1-a-receptor-for-the-porcine-endogenous-retrovirus-a-perv-a-play-a-critical-role-in-cell-surface-expression-and-infectivity
#1
Winston Colon-Moran, Takele Argaw, Carolyn A Wilson
Porcine endogenous retrovirus-A (PERV-A), a gammaretrovirus, infects human cells in vitro, thus raising the potential risk of cross-species transmission in xenotransplantation. Two members of the solute carrier family 52 (SLC52A1 and SLC52A2) are PERV-A receptors. Site-directed mutagenesis of the cDNA encoding SLC52A1 identified that only one of two putative glycosylation signals is occupied by glycans. In addition, we showed that glycosylation of SLC52A1 is not necessary for PERV-A receptor function. We also identified that at a minimum, three cysteine residues are sufficient for SLC52A1 cell surface expression...
April 20, 2017: Virology
https://www.readbyqxmd.com/read/28436965/a-three-dimensional-model-of-human-lung-development-and-disease-from-pluripotent-stem-cells
#2
Ya-Wen Chen, Sarah Xuelian Huang, Ana Luisa Rodrigues Toste de Carvalho, Siu-Hong Ho, Mohammad Naimul Islam, Stefano Volpi, Luigi D Notarangelo, Michael Ciancanelli, Jean-Laurent Casanova, Jahar Bhattacharya, Alice F Liang, Laura M Palermo, Matteo Porotto, Anne Moscona, Hans-Willem Snoeck
Recapitulation of lung development from human pluripotent stem cells (hPSCs) in three dimensions (3D) would allow deeper insight into human development, as well as the development of innovative strategies for disease modelling, drug discovery and regenerative medicine. We report here the generation from hPSCs of lung bud organoids (LBOs) that contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel 3D culture. Expression analysis and structural features indicated that the branching structures reached the second trimester of human gestation...
April 24, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28433740/xenotransplantation-of-layer-by-layer-encapsulated-non-human-primate-islets-with-a-specified-immunosuppressive-drug-protocol
#3
Muhammad R Haque, Jiwoong Kim, Hyojun Park, Han Sin Lee, Kyo Won Lee, Taslim A Al-Hilal, Jee-Heon Jeong, Cheol-Hee Ahn, Doo Sung Lee, Sung Joo Kim, Youngro Byun
Islet transplantation is as effective as but also less immunogenic than pancreas transplantation for the treatment of type 1 diabetes mellitus. However, as the complete elimination of immunogenicity still remains a major obstacle in islet transplantation, layer-by-layer encapsulation (LbL) of pancreatic islets using biocompatible polymers offers a rational approach to reducing host immune response towards transplanted islets. We investigated the effect of LbL of non-human primate (NHP) islets on reducing immunogenicity as a preclinical model since NHPs have close phylogenetic and immunological relationship with human...
April 19, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28432704/human-galectin-9-on-the-porcine-cells-affects-the-cytotoxic-activity-of-m1-differentiated-thp-1-cells-through-inducing-a-shift-in-m2-differentiated-thp-1-cells
#4
Sung Han Jung, Jeong Ho Hwang, Sang Eun Kim, Young Kyu Kim, Hyo Chang Park, Hoon Taek Lee
BACKGROUND: In xenotransplantation, immune rejection by macrophages occurs rapidly and remains a major obstacle. Studies to control immune rejection in macrophages have been continuing to date. Recent studies have reported that human galectin-9 (hGal-9) can regulate the function of regulatory T cells (Treg), as well as cytotoxicity T cells (CTL) and natural killer cells (NK). Although the effect of hGal-9 on lymphocytes has been well studied, the relationship between hGal-9 and myeloid cells has been scarcely studied...
April 21, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28425928/porcine-circoviruses-and-xenotransplantation
#5
REVIEW
Joachim Denner, Annette Mankertz
Allotransplantation and xenotransplantation may be associated with the transmission of pathogens from the donor to the recipient. Whereas in the case of allotransplantation the transmitted microorganisms and their pathogenic effect are well characterized, the possible influence of porcine microorganisms on humans is mostly unknown. Porcine circoviruses (PCVs) are common in pig breeds and they belong to porcine microorganisms that still have not been fully addressed in terms of evaluating the potential risk of xenotransplantation using pig cells, tissues, and organs...
April 20, 2017: Viruses
https://www.readbyqxmd.com/read/28423357/mir-29b-inhibits-the-growth-of-glioma-via-mycn-dependent-way
#6
Guan Sun, Jingmin Lu, Chuang Zhang, Ran You, Lei Shi, Nan Jiang, Dekang Nie, Jian Zhu, Min Li, Jun Guo
MiR-29b is widely involved in diverse cancers. We plan to study its role in glioma. The expression of miR-29b was detected by real-time polymerase chain reaction (PCR) and we found the expression of miR-29b was decreased in glioma. Cell proliferation was evaluated by cell counting kit (CCK8) and 5-Ethynyl-2'- deoxyuridine (EdU) and cell apoptosis was assayed with flow cytometry assay (FCA), which indicated miR-29b can inhibit the proliferation and promote the apoptosis of glioma cells. The target of miR-29b was predicted using miRanda, TargetScan and PicTar sofeware and we also found MYCN was a direct target of miR-29b in glioma cells and miR-29b inhibited the proliferation of glioma cells via MYCN dependent way...
April 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421681/early-clinical-xenotransplantation-experiences-an-interview-with-thomas-e-starzl-md-phd
#7
REVIEW
David K C Cooper
Dr Thomas E. Starzl, who died on March 4, 2017, was one of the great pioneers of organ transplantation. He was also a pioneer in the field of xenotransplantation. In 1964, he carried out baboon kidney transplants in six patients with terminal renal disease for whom no living or deceased donor became available; graft survival was for 19-60 days, the grafts being lost largely through continuous complement activation. Between 1966 and 1974, he carried out one ex vivo liver perfusion and three orthotopic liver transplants using chimpanzees as sources of organs; graft survival was for <14 days...
March 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28421679/thomas-starzl-visionary-and-xenotransplantation-pioneer-commentary-from-the-international-xenotransplant-association-vanguard-committee
#8
Wayne J Hawthorne, Arielle Cimeno, Mohamed Ezzelarab, Bynvant Sandhu, Christopher Burlak
No abstract text is available yet for this article.
March 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28418910/erythropoietin-drives-breast-cancer-progression-by-activation-of-its-receptor-epor
#9
Ka Kui Chan, Kyle B Matchett, Jonathan A Coulter, Hiu-Fung Yuen, Cian M McCrudden, Shu-Dong Zhang, Gareth W Irwin, Matthew A Davidson, Thomas Rülicke, Sophie Schober, Ludger Hengst, Heidelinde Jaekel, Angela Platt-Higgins, Philip S Rudland, Ken I Mills, Perry Maxwell, Mohamed El-Tanani, Terence R Lappin
Breast cancer is a leading cause of cancer-related deaths. Anemia is common in breast cancer patients and can be treated with blood transfusions or with recombinant erythropoietin (EPO) to stimulate red blood cell production. Clinical studies have indicated decreased survival in some groups of cancer patients treated with EPO. Numerous tumor cells express the EPO receptor (EPOR), posing a risk that EPO treatment would enhance tumor growth, but the mechanisms involved in breast tumor progression are poorly understood...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415590/multiple-anti-tumor-effects-of-reparixin-on-thyroid-cancer
#10
Federica Liotti, Maria De Pizzol, Marcello Allegretti, Nella Prevete, Rosa Marina Melillo
BACKGROUND: Expression of IL-8 and its receptors CXCR1 and CXCR2 is a common occurrence in human epithelial thyroid cancer (TC). In human TC samples, IL-8 expression is associated with tumor progression. IL-8 enhances proliferation, survival, motility, and leads to the maintenance of stemness features and tumor-initiating ability of TC cells. Here, we studied the effects of Reparixin (formerly Repertaxin), a small molecular weight CXCR1 and CXCR2 inhibitor, on the malignant phenotype of various TC cell lines...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414310/autophagy-supports-generation-of-cells-with-high-cd44-expression-via-modulation-of-oxidative-stress-and-parkin-mediated-mitochondrial-clearance
#11
K A Whelan, P M Chandramouleeswaran, K Tanaka, M Natsuizaka, M Guha, S Srinivasan, D S Darling, Y Kita, S Natsugoe, J D Winkler, A J Klein-Szanto, R K Amaravadi, N G Avadhani, A K Rustgi, H Nakagawa
High CD44 expression is associated with enhanced malignant potential in esophageal squamous cell carcinoma (ESCC), among the deadliest of all human carcinomas. Although alterations in autophagy and CD44 expression are associated with poor patient outcomes in various cancer types, the relationship between autophagy and cells with high CD44 expression remains incompletely understood. In transformed oesophageal keratinocytes, CD44(Low)-CD24(High) (CD44L) cells give rise to CD44(High)-CD24(-/Low) (CD44H) cells via epithelial-mesenchymal transition (EMT) in response to transforming growth factor (TGF)-β...
April 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28397982/generation-of-chimeric-minipigs-by-aggregating-4-to-8-cell-stage-blastomeres-from-somatic-cell-nuclear-transfer-with-the-tracing-of-enhanced-green-fluorescent-protein
#12
Huili Ji, Chuan Long, Chong Feng, Ningning Shi, Yingdi Jiang, Guomin Zeng, Xirui Li, Jingjing Wu, Lin Lu, Shengsheng Lu, Dengke Pan
BACKGROUND: Blastocyst complementation is an important technique for generating chimeric organs in organ-deficient pigs, which holds great promise for solving the problem of a shortage of organs for human transplantation procedures. Porcine chimeras have been generated using embryonic germ cells, embryonic stem cells, and induced pluripotent stem cells; however, there are no authentic pluripotent stem cells for pigs. In previous studies, blastomeres from 4- to 8-cell-stage parthenogenetic embryos were able to generate chimeric fetuses efficiently, but the resulting fetuses did not produce live-born young...
April 11, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28397351/the-resurgence-of-xenotransplantation
#13
Peter J Cowan, A Joseph Tector
There has been an upsurge of interest in xenotransplantation in recent years. This resurgence can attributed to a combination of factors. First, there has been a dramatic improvement in efficacy in several preclinical models, with maximum xenograft survival times increasing to 950 days for islets, 945 days for hearts, and 310 days for kidneys. Second, the rapid development of genome editing technology (particularly the advent of CRISPR/Cas9) has revolutionized the capacity to generate new donor pigs with multiple protective genetic modifications; what once took many years to achieve can now be performed in months, with much greater precision and scope...
April 11, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28396495/clonal-selection-and-asymmetric-distribution-of-human-leukemia-in-murine-xenografts-revealed-by-cellular-barcoding
#14
Mirjam E Belderbos, Taco Koster, Bertien Ausema, Sabrina Jacobs, Sharlaine Sowdagar, Erik Zwart, Eveline de Bont, Gerald de Haan, Leonid V Bystrykh
Genetic and phenotypic heterogeneity of human leukemia is thought to drive leukemia progression through a Darwinian process of selection and evolution of increasingly malignant clones. However, the lack of markers to uniquely identify individual leukemia clones precludes high resolution tracing of their clonal dynamics. Here, we employ cellular barcoding to analyze the clonal behavior of patient-derived leukemia-propagating cells (LPCs) in murine xenografts. Using a leukemic cell line and diagnostic bone marrow cells from six patients with B-progenitor cell acute lymphoblastic leukemia (B-ALL), we demonstrate that patient-derived xenografts were highly polyclonal, consisting of tens to hundreds of LPC clones...
April 10, 2017: Blood
https://www.readbyqxmd.com/read/28393447/anti-cd40-antibody-mediated-costimulation-blockade-promotes-long-term-survival-of-deep-lamellar-porcine-corneal-grafts-in-non-human-primates
#15
Jaeyoung Kim, Dong Hyun Kim, Hyuk Jin Choi, Hyun Ju Lee, Hee Jung Kang, Chung-Gyu Park, Eung-Soo Hwang, Mee Kum Kim, Won Ryang Wee
BACKGROUND: Corneal xenotransplantation is an effective solution for the shortage of human donor corneas, and the porcine cornea may be a suitable candidate for the donor cornea because of its optical similarity with humans. However, it is necessary to administer additional immunosuppressants to overcome antigenic differences. We aimed to investigate the feasibility of porcine corneas with anti-CD40 antibody-mediated costimulation blockade in a clinically applicable pig-to-non-human primate corneal xenotransplantation model...
April 10, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28393401/the-potentiating-effect-of-htfpi-in-the-presence-of-hcd47-reduces-the-cytotoxicity-of-human-macrophages
#16
Sung Han Jung, Jeong Ho Hwang, Sang Eun Kim, Kim Young Kyu, Hyo Chang Park, Hoon Taek Lee
BACKGROUND: In pig-to-human xenotransplantation, hyperacute rejection of pig organs could be overcome by the production of α1,3-galactosyltransferase knockout pigs. However, macrophage-mediated acute rejection is another obstacle that needs to be overcome. Among the various candidate genes involved in acute rejection, CD47 inhibits monocyte/macrophage-mediated phagocytosis by identifying the CD47 signal regulatory protein alpha (SIRP-α) as self/non-self. Tissue factor pathway inhibitor (TFPI) is involved in the regulation of the coagulation pathway and is able to bind to another ligand of CD47, thrombospondin-1 (TSP-1)...
April 10, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28389406/simultaneous-overexpression-of-human-e5nt-and-entpd1-protects-porcine-endothelial-cells-against-h2o2-induced-oxidative-stress-and-cytotoxicity-in-vitro
#17
Elisa Chisci, Marco De Giorgi, Elisa Zanfrini, Angela Testasecca, Elena Brambilla, Alessandro Cinti, Laura Farina, Barbara Kutryb-Zajac, Cristina Bugarin, Chiara Villa, Emanuela Grassilli, Romina Combi, Giuseppe Gaipa, Maria Grazia Cerrito, Ilaria Rivolta, Ryszard Tomasz Smolenski, Marialuisa Lavitrano, Roberto Giovannoni
Ischemia-reperfusion injury (IRI) and oxidative stress still limit the survival of cells and organs in xenotransplantation models. Ectonucleotidases play an important role in inflammation and IRI in transplantation settings. We tested the potential protective effects derived by the co-expression of the two main vascular ectonucleotidases, ecto-5'-nucleotidase (E5NT) and ecto nucleoside triphosphate diphosphohydrolase 1 (ENTPD1), in an in vitro model of H2O2-induced oxidative stress and cytotoxicity. We produced a dicistronic plasmid (named pCX-DI-2A) for the co-expression of human E5NT and ENTPD1 by using the F2A technology...
April 5, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28386960/xenotransplantation-literature-update-january-february-2017
#18
Karl Kerns, AnAn Hua, Christopher Burlak
No abstract text is available yet for this article.
April 6, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28386296/high-risk-gastrointestinal-stromal-tumour-gist-and-synovial-sarcoma-display-similar-angiogenic-profiles-a-nude-mice-xenograft-study
#19
Francisco Giner, Isidro Machado, Jose Antonio Lopez-Guerrero, Empar Mayordomo-Aranda, Antonio Llombart-Bosch
BACKGROUND: Gastrointestinal stromal tumour (GIST) is the most common primary mesenchymal tumour of the gastrointestinal tract. Spindle cell monophasic synovial sarcoma (SS) can be morphologically similar. Angiogenesis is a major factor for tumour growth and metastasis. Our aim was to compare the angiogenic expression profiles of high-risk GIST and spindle cell monophasic SS by histological, immunohistochemical and molecular characterisation of the neovascularisation established between xenotransplanted tumours and the host during the initial phases of growth in nude mice...
2017: Ecancermedicalscience
https://www.readbyqxmd.com/read/28322428/xenotransplantation-where-do-we-stand-in-2016
#20
Gisella L Puga Yung, Robert Rieben, Leo Bühler, Henk-Jan Schuurman, Jörg Seebach
Worldwide, there is a constant rise in the number of patients with end-stage organ failure in critical need for transplants, but the number of organs/cells available from deceased or living human donors is limited. Xenotransplantation using pig organs/tissues repre-sents a potential solution for this shortage; however, it has been hampered by a number of mainly immuno-logical hurdles. Remarkable progress was presented at the latest biennial (13th) international congress of the International Xenotransplantation Association, November 2015 in Melbourne, Australia, and the American Transplant Congress, May 2016 in Boston, USA...
March 21, 2017: Swiss Medical Weekly
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