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Xenotransplantation

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https://www.readbyqxmd.com/read/28103265/rabbit-model-of-human-gliomas-implications-for-intra-arterial-drug-delivery
#1
Huamin Qin, Miroslaw Janowski, Monica S Pearl, Izabela Malysz-Cymborska, Shen Li, Charles G Eberhart, Piotr Walczak
The prognosis for malignant brain tumors remains poor despite a combination of surgery, radiotherapy, and chemotherapy. This is partly due to the blood-brain barrier, a major obstacle that prevents therapeutic agents from effectively reaching the tumor. We have recently developed a method for precise and predictable opening of the blood-brain barrier via the intra-arterial administration of mannitol, a hyperosmolar agent, in a rabbit model, whose vascular anatomy facilitates the use of standard interventional neuroradiology techniques and devices...
2017: PloS One
https://www.readbyqxmd.com/read/28101175/effect-of-mir-146a-and-mir-155-on-cardiac-xenotransplantation
#2
Zhicheng Zhao, Feng Qi, Tong Liu, Weihua Fu
The aim of the present study was to investigate the expression levels of miR-146a and miR-155 in a cardiac xenograft model treated with the immunosuppressant FK506, and to construct lentiviral vectors to further study the roles of miR-146a and miR-155 in cardiac xenotransplantation. Expression levels of miR-146a and miR-155 were examined by quantitative polymerase chain reaction analysis and protein expression of RelA, which is a member of the nuclear factor-κB family, was examined by western blot analysis...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28099406/reducing-the-threshold-for-clinical-renal-xenotransplantation
#3
Peter J Cowan, Francesco L Ierino
No abstract text is available yet for this article.
January 17, 2017: Transplantation
https://www.readbyqxmd.com/read/28075522/crucial-role-of-carbonic-anhydrase-ix-in-tumorigenicity-of-xenotransplanted-adult-t-cell-leukemia-derived-cells
#4
Kentaro Nasu, Kazunori Yamaguchi, Tomoka Takanashi, Keiichi Tamai, Ikuro Sato, Shoji Ine, Osamu Sasaki, Kennichi Satoh, Nobuyuki Tanaka, Yuetsu Tanaka, Takuya Fukushima, Hideo Harigae, Kazuo Sugamura
Carbonic anhydrase IX (CA9) is a membrane-associated carbonic anhydrase that regulates cellular pH, is upregulated in various solid tumors, and is considered to be a therapeutic target. Here, we describe the essential role of CA9 in the tumorigenicity of cells derived from human adult T-cell leukemia/lymphoma (ATL). We previously established the highly tumorigenic ST1-N6 subline from the ATL-derived ST1 cell line by serial xenotransplantation in NOG mice. In the present study, we first show that CA9 expression is strongly enhanced in ST1-N6 cells...
January 11, 2017: Cancer Science
https://www.readbyqxmd.com/read/28063039/xenotransplantation-model-of-psoriasis
#5
Jeremy Di Domizio, Curdin Conrad, Michel Gilliet
Psoriasis is a chronic autoimmune skin disease affecting approximately 2 % of the population with a major psychosocial and socioeconomic impact. A causal therapy leading to permanent cure is not available, and current treatments only lead to limited amelioration, and therefore new therapeutic targets need to be identified. Recent works demonstrated a predominant role of TH17 cells in the pathogenesis of psoriasis; yet the underlying molecular mechanisms driving the development of the disease are still largely elusive...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28058735/safe-use-of-anti-cd154-monoclonal-antibody-in-pig-islet-xenotransplantation-in-monkeys
#6
Rita Bottino, Michael F Knoll, Joshua Graeme-Wilson, Edwin C Klein, David Ayares, Massimo Trucco, David K C Cooper
Anti-CD154mAb is a powerful co-stimulation blockade agent that is efficacious in preventing rejection, even in xenogeneic settings. It has been used in the majority of successful long-term pig-to-non-human primate islet transplantation models. However, its clinical use was halted as a result of thromboembolic complications that were also observed in preclinical and clinical organ transplantation models. An anti-CD154mAb was administered to 14 streptozotocin-induced diabetic cynomolgus monkey recipients of porcine islets, some of which received the agent for many months...
January 6, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28054735/initial-study-of-%C3%AE-1-3-galactosyltransferase-gene-knockout-cd46-pig-full-thickness-corneal-xenografts-in-rhesus-monkeys
#7
Xiaojuan Dong, Hidetaka Hara, Ying Wang, Li Wang, Yingnan Zhang, David K C Cooper, Yifan Dai, Zhiqiang Pan
BACKGROUND: To investigate graft survival after full-thickness corneal xenotransplantation from α1,3-galactosyltransferase gene-knockout (GTKO) pigs expressing a human complement regulatory protein (GTKO/CD46 pigs) in rhesus monkeys. METHODS: Rhesus monkeys (n=10) were transplanted with full-thickness corneas from wild-type (WT; n=4) and GTKO/CD46 (n=4) pigs or from monkeys (n=2). All recipient monkeys received post-transplant subconjunctival injections of betamethasone...
January 5, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28027893/correction-of-recessive-dystrophic-epidermolysis-bullosa-by-transposon-mediated-integration-of-col7a1-in-transplantable-patient-derived-primary-keratinocytes
#8
Maria Carmela Latella, Fabienne Cocchiarella, Laura De Rosa, Giandomenico Turchiano, Manuel A F V Gonçalves, Fernando Larcher, Michele De Luca, Alessandra Recchia
Recessive dystrophic epidermolysis bullosa (RDEB) is caused by defects in type-VII collagen (C7), a protein encoded by the COL7A1 gene and essential for anchoring fibril formation at the dermal-epidermal junction. Gene therapy of RDEB is based on transplantation of autologous epidermal grafts generated from gene-corrected keratinocytes sustaining C7 deposition at the dermal-epidermal junction. Transfer of the COL7A1 gene is complicated by its very large size and repetitive sequence. We report a gene delivery approach based on the Sleeping beauty transposon, which allows integration of a full-length COL7A1 cDNA and secretion of C7 at physiological levels in RDEB keratinocytes without rearrangements or detrimental effects on their clonogenic potential...
December 24, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28008146/autologous-reconstitution-of-human-cancer-and-immune-system-in-vivo
#9
Juan Fu, Rupashree Sen, David L Masica, Rachel Karchin, Drew Pardoll, Vonn Walter, D Neil Hayes, Christine H Chung, Young J Kim
Correlative studies from checkpoint inhibitor trials have indicated that better understanding of human leukocytic trafficking into the human tumor microenvironment can expedite the translation of future immune-oncologic agents. In order to directly characterize signaling pathways that can regulate human leukocytic trafficking into the tumor, we have developed a completely autologous xenotransplantation method to reconstitute the human tumor immune microenvironment in vivo. We were able to genetically mark the engrafted CD34+ bone marrow cells as well as the tumor cells, and follow the endogenous leukocytic infiltration into the autologous tumor...
December 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/28006930/systemic-administration-of-mirna-mimics-by-liposomal-delivery-system-in-animal-model-of-colorectal-carcinoma
#10
J Merhautová, P Vychytilová-Faltejsková, R Demlová, O Slabý
MiRNAs are important regulators of gene expression and changes in their levels are linked with various pathological states, including solid tumors. MiR-215 has been identified as a tumor suppressor in colorectal cancer (CRC). Following our previous in vitro and in vivo experiments, the aim of this project was to study the possibility of increasing the levels of miR-215 in tumor cells by systemic administration of miRNA mimics in liposomal delivery system in vivo. By subcutaneous xenotransplantation of human cancer cells to NSG mice, CRC model was established...
December 21, 2016: Physiological Research
https://www.readbyqxmd.com/read/27999419/transspecies-transmission-of-gammaretroviruses-and-the-origin-of-the-gibbon-ape-leukaemia-virus-galv-and-the-koala-retrovirus-korv
#11
REVIEW
Joachim Denner
Transspecies transmission of retroviruses is a frequent event, and the human immunodeficiency virus-1 (HIV-1) is a well-known example. The gibbon ape leukaemia virus (GaLV) and koala retrovirus (KoRV), two gammaretroviruses, are also the result of a transspecies transmission, however from a still unknown host. Related retroviruses have been found in Southeast Asian mice although the sequence similarity was limited. Viruses with a higher sequence homology were isolated from Melomys burtoni, the Australian and Indonesian grassland melomys...
December 20, 2016: Viruses
https://www.readbyqxmd.com/read/27982048/efficient-generation-of-b2m-null-pigs-via-injection-of-zygote-with-talens
#12
Yong Wang, Yinan Du, Xiaoyang Zhou, Lulu Wang, Jian Li, Fengchao Wang, Zhengen Huang, Xingxu Huang, Hong Wei
Donor major histocompatibility complex class I (MHC I) molecules are the main targets of the host immune response after organ allotransplantation. Whether and how MHC I-deficiency of pig donor tissues affects rejection after xenotransplantation has not been assessed. Beta2-microglobulin (B2M) is indispensable for the assembly of MHC I receptors and therefore provides an effective target to disrupt cell surface MHC I expression. Here, we report the one-step generation of mutant pigs with targeted disruptions in B2m by injection of porcine zygotes with B2m exon 2-specific TALENs...
December 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27935045/patient-derived-xenografts-of-gastrointestinal-cancers-are-susceptible-to-rapid-and-delayed-b-lymphoproliferation
#13
Sebastian M Dieter, Klara M Giessler, Mark Kriegsmann, Taronish D Dubash, Lino Möhrmann, Erik R Schulz, Christine Siegl, Sarah Weber, Hendrik Strakerjahn, Ava Oberlack, Ulrike Heger, Jianpeng Gao, Eva-Maria Hartinger, Felix Oppel, Christopher M Hoffmann, Nati Ha, Benedikt Brors, Felix Lasitschka, Alexis Ulrich, Oliver Strobel, Manfred Schmidt, Christof von Kalle, Martin Schneider, Wilko Weichert, K Roland Ehrenberg, Hanno Glimm, Claudia R Ball
Patient-derived cancer xenografts (PDX) are widely used to identify and evaluate novel therapeutic targets, and to test therapeutic approaches in preclinical mouse avatar trials. Despite their widespread use, potential caveats of PDX models remain considerably underappreciated. Here, we demonstrate that EBV-associated B-lymphoproliferations frequently develop following xenotransplantation of human colorectal and pancreatic carcinomas in highly immunodeficient NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl) /SzJ (NSG) mice (18/47 and 4/37 mice, respectively), and in derived cell cultures in vitro...
December 9, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27931512/xenotransplanted-pig-sertoli-cells-inhibit-both-the-alternative-and-classical-pathways-of-complement-mediated-cell-lysis-while-pig-islets-are-killed
#14
Kandis Wright, Rachel Dziuk, Payal Mital, Gurvinder Kaur, Jannette M Dufour
Xenotransplantation has vast clinical potential but is limited by the potent immune responses generated against xenogeneic tissue. Immune-privileged Sertoli cells (SCs) survive xenotransplantation long term (90 days) without immunosuppression, making SCs an ideal model to identify xenograft survival mechanisms. Xenograft rejection includes the binding of natural and induced antibodies and the activation of the complement cascade. Using an in vitro cytotoxicity assay, wherein cells were cultured with human serum and complement, we demonstrated that neonatal pig SCs (NPSCs) are resistant to complement-mediated cell lysis and express complement inhibitory factors, membrane cofactor protein (MCP; CD46), and decay-accelerating factor (DAF; CD55) at significantly higher levels than neonatal pig islets (NPIs), which served as non-immune-privileged controls...
November 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27926740/a-17-gene-stemness-score-for-rapid-determination-of-risk-in-acute-leukaemia
#15
Stanley W K Ng, Amanda Mitchell, James A Kennedy, Weihsu C Chen, Jessica McLeod, Narmin Ibrahimova, Andrea Arruda, Andreea Popescu, Vikas Gupta, Aaron D Schimmer, Andre C Schuh, Karen W Yee, Lars Bullinger, Tobias Herold, Dennis Görlich, Thomas Büchner, Wolfgang Hiddemann, Wolfgang E Berdel, Bernhard Wörmann, Meyling Cheok, Claude Preudhomme, Herve Dombret, Klaus Metzeler, Christian Buske, Bob Löwenberg, Peter J M Valk, Peter W Zandstra, Mark D Minden, John E Dick, Jean C Y Wang
Refractoriness to induction chemotherapy and relapse after achievement of remission are the main obstacles to cure in acute myeloid leukaemia (AML). After standard induction chemotherapy, patients are assigned to different post-remission strategies on the basis of cytogenetic and molecular abnormalities that broadly define adverse, intermediate and favourable risk categories. However, some patients do not respond to induction therapy and another subset will eventually relapse despite the lack of adverse risk factors...
December 15, 2016: Nature
https://www.readbyqxmd.com/read/27923030/patient-derived-induced-pluripotent-stem-cells-in-cancer-research-and-precision-oncology
#16
Eirini P Papapetrou
Together with recent advances in the processing and culture of human tissue, bioengineering, xenotransplantation and genome editing, Induced pluripotent stem cells (iPSCs) present a range of new opportunities for the study of human cancer. Here we discuss the main advantages and limitations of iPSC modeling, and how the method intersects with other patient-derived models of cancer, such as organoids, organs-on-chips and patient-derived xenografts (PDXs). We highlight the opportunities that iPSC models can provide beyond those offered by existing systems and animal models and present current challenges and crucial areas for future improvements toward wider adoption of this technology...
December 6, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27914702/renal-xenotransplantation-experimental-progress-and-clinical-prospects
#17
Martin Wijkstrom, Hayato Iwase, Wayne Paris, Hidetaka Hara, Mohamed Ezzelarab, David K C Cooper
There are >100,000 patients waiting for kidney transplants in the United States and a vast need worldwide. Xenotransplantation, in the form of the transplantation of kidneys from genetically engineered pigs, offers the possibility of overcoming the chronic shortage of deceased and living human donors. These genetic manipulations can take the form of (i) knockout of pig genes that are responsible for the expression of antigens against which the primate (human or nonhuman primate) has natural "preformed" antibodies that bind and initiate complement-mediated destruction or (ii) the insertion of human transgenes that provide protection against the human complement, coagulation, or inflammatory responses...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27906824/selection-of-patients-for-initial-clinical-trials-of-solid-organ-xenotransplantation
#18
David K C Cooper, Martin Wijkstrom, Sundaram Hariharan, Joshua L Chan, Avneesh Singh, Keith Horvath, Muhammad Mohiuddin, Arielle Cimeno, Rolf N Barth, John C LaMattina, Richard N Pierson
Several groups have reported extended survival of genetically-engineered pig organs in nonhuman primates, varying from almost 10 months for life-supporting kidney grafts and >2 years for nonlife-supporting heart grafts to less than 1 month for life-supporting liver and lung grafts. We have attempted to define groups of patients who may not have an option to wait for an allograft. These include kidney, heart, and lung candidates who are highly-allosensitized. In addition, some kidney candidates (who have previously lost at least 2 allografts from rapid recurrence of native kidney disease) have a high risk of further recurrence and will not be offered a repeat allotransplant...
December 1, 2016: Transplantation
https://www.readbyqxmd.com/read/27897334/xenotransplantation-literature-update-september-october-2016
#19
AnAn Hua, Magie Steinhoff, Christopher Burlak
No abstract text is available yet for this article.
November 2016: Xenotransplantation
https://www.readbyqxmd.com/read/27892637/distribution-of-follicles-in-canine-ovarian-tissues-and-xenotransplantation-of-cryopreserved-ovarian-tissues-with-even-distribution-of-follicles
#20
I Wakasa, M Hayashi, Y Abe, H Suzuki
Ovarian follicles are not homogeneously distributed within the ovarian cortex in several species of mammals. Yet to maximize the reproducibility of experimental results of ovarian transplantation, it is essential to assess the degree of density and distribution of follicles in ovarian tissues before their transplantation. In this study, the ovarian cortex from 13 immature bitches (ten purebred and three mongrels) was sectioned into 1.0- to 1.5-mm(3) cubes, those were fixed, sectioned and stained with haematoxylin and eosin...
November 28, 2016: Reproduction in Domestic Animals, Zuchthygiene
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