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Ann M. Arvin - One of the best experts on this subject based on the ideXlab platform.
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Varicella-Zoster Virus Neurotropism in SCID Mouse–Human Dorsal Root Ganglia Xenografts
Current Topics in Microbiology and Immunology, 2010Co-Authors: Leigh Zerboni, Mike Reichelt, Ann M. ArvinAbstract:Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus and the causative agent of varicella and herpes zoster. VZV reactivation from latency in sensory nerve ganglia is a direct consequence of VZV neurotropism. Investigation of VZV neuropathogenesis by infection of human dorsal root ganglion xenografts in immunocompromised (SCID) mice has provided a novel system in which to examine VZV neurotropism. Experimental infection with recombinant VZV mutants with targeted deletions or mutations of specific genes or regulatory elements provides an opportunity to assess gene candidates that may mediate neurotropism and neurovirulence. The SCID Mouse–human DRG xenograft model may aid in the development of clinical strategies in the management of herpes zoster as well as in the development of “second generation” neuroattenuated vaccines.
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varicella zoster virus neurotropism in SCID Mouse human dorsal root ganglia xenografts
Current Topics in Microbiology and Immunology, 2010Co-Authors: Leigh Zerboni, Mike Reichelt, Ann M. ArvinAbstract:Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus and the causative agent of varicella and herpes zoster. VZV reactivation from latency in sensory nerve ganglia is a direct consequence of VZV neurotropism. Investigation of VZV neuropathogenesis by infection of human dorsal root ganglion xenografts in immunocompromised (SCID) mice has provided a novel system in which to examine VZV neurotropism. Experimental infection with recombinant VZV mutants with targeted deletions or mutations of specific genes or regulatory elements provides an opportunity to assess gene candidates that may mediate neurotropism and neurovirulence. The SCID Mouse–human DRG xenograft model may aid in the development of clinical strategies in the management of herpes zoster as well as in the development of “second generation” neuroattenuated vaccines.
Leigh Zerboni - One of the best experts on this subject based on the ideXlab platform.
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Varicella-Zoster Virus Neurotropism in SCID Mouse–Human Dorsal Root Ganglia Xenografts
Current Topics in Microbiology and Immunology, 2010Co-Authors: Leigh Zerboni, Mike Reichelt, Ann M. ArvinAbstract:Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus and the causative agent of varicella and herpes zoster. VZV reactivation from latency in sensory nerve ganglia is a direct consequence of VZV neurotropism. Investigation of VZV neuropathogenesis by infection of human dorsal root ganglion xenografts in immunocompromised (SCID) mice has provided a novel system in which to examine VZV neurotropism. Experimental infection with recombinant VZV mutants with targeted deletions or mutations of specific genes or regulatory elements provides an opportunity to assess gene candidates that may mediate neurotropism and neurovirulence. The SCID Mouse–human DRG xenograft model may aid in the development of clinical strategies in the management of herpes zoster as well as in the development of “second generation” neuroattenuated vaccines.
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varicella zoster virus neurotropism in SCID Mouse human dorsal root ganglia xenografts
Current Topics in Microbiology and Immunology, 2010Co-Authors: Leigh Zerboni, Mike Reichelt, Ann M. ArvinAbstract:Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus and the causative agent of varicella and herpes zoster. VZV reactivation from latency in sensory nerve ganglia is a direct consequence of VZV neurotropism. Investigation of VZV neuropathogenesis by infection of human dorsal root ganglion xenografts in immunocompromised (SCID) mice has provided a novel system in which to examine VZV neurotropism. Experimental infection with recombinant VZV mutants with targeted deletions or mutations of specific genes or regulatory elements provides an opportunity to assess gene candidates that may mediate neurotropism and neurovirulence. The SCID Mouse–human DRG xenograft model may aid in the development of clinical strategies in the management of herpes zoster as well as in the development of “second generation” neuroattenuated vaccines.
Ulf Müller-ladner - One of the best experts on this subject based on the ideXlab platform.
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The therapeutic use of osmotic minipumps in the severe combined immunodeficiency (SCID) Mouse model for rheumatoid arthritis
Annals of the rheumatic diseases, 2008Co-Authors: Anette Knedla, Ulf Müller-ladner, Birgit Riepl, Stephanie Lefèvre, S Kistella, Joachim Grifka, Rainer H. Straub, J. Schölmerich, Elena NeumannAbstract:Objectives: The viral gene transfer of Interleukin-1 receptor antagonist (IL-1ra) and Interleukin-10 (IL-10) into rheumatoid arthritis (RA) synovial fibroblasts (RASF) showed protective effects on cartilage destruction in the SCID Mouse model for RA. Nevertheless, side effects of viral transduction are possible and a number of cytokines or cytokine inhibitors are not available encoded in viral vehicles. As the production of viruses coding for bioactive proteins is cost- and time-intensive, we established an in vivo long-term release model using osmotic minipumps in the SCID Mouse model for RA. Methods: Isolated RASF were cultured for 4 passages and coimplanted together with human cartilage and an Alzet® Osmotic Miniature Pump Model 2004 containing 200 µl of IL-10 and IL-1ra for 40 days in SCID mice. Implants were removed after 40 days and evaluated histologically. The actual rates of IL-10 and IL-1ra in murine serum were measured by ELISA. Results: Release of IL-10 and IL-1ra by the pumps was effective as both could be measured in significant amounts in the serum of the mice. IL-10 and IL-1ra release showed protective effects towards the co-implanted cartilage, similar to the adenovirally IL-10-/IL-1ra-transduced RASF. The invasion scores for the implants with the osmotic pumps were: invasion 0.7±0.5, degradation 0.5±0.3 (all parameters significant vs. controls, p Conclusions: The results demonstrate that the combination of osmotic pumps with the SCID Mouse model for RA can be used as approach for application and evaluation of cartilage-protective molecules. Furthermore, the effect of cartilage-protective cytokines is independent of the type of application.
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Gene transfer to synovial fibroblast: methods and evaluation in the SCID Mouse model.
Methods in molecular medicine, 2007Co-Authors: Ingmar Meinecke, Ulf Müller-ladner, Edita Rutkauskaite, Antje Cinski, Thomas PapAbstract:The use of gene transfer techniques has become of utmost importance both for the analysis of molecular pathways of rheumatic joint destruction and for the evaluation of novel therapeutic concepts to treat rheumatic diseases. However, gene transfer into synovial fibroblasts faces several challenges, which result mainly from the lack of specific surface markers and the low-proliferation rate of these cells. This chapter describes both nonviral and viral strategies of transferring gene constructs into synovial fibroblasts. It focuses on the use of lipofection for the gene transfer of siRNA to synovial fibroblasts and the use of AMAXA-nucleofection for the nonviral transfer of gene expression constructs. In addition, retro- and lentiviral strategies of gene transfer are introduced. Finally, the SCID Mouse in vivo model of rheumatoid joint destruction is described as a means of evaluating the effects of gene transfer on the invasiveness of synovial fibroblasts.
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The SCID Mouse model: novel therapeutic targets – lessons from gene transfer
Springer seminars in immunopathology, 2003Co-Authors: Matthias Pierer, Ulf Müller-ladner, Thomas Pap, Michel NeidhartAbstract:The hallmark of rheumatoid arthritis (RA) is progressive destruction of the joints, preceded and accompanied by synovial hyperplasia and chronic inflammation. Spontaneous and induced animal models of RA reflect predominantly the inflammatory aspects of the disease. To reproduce the destruction of cartilage and bone mediated by an activated synovium, it was desirable to develop models that allow the dissection of cellular and molecular components derived from human tissue. The SCID Mouse co-implantation model of human RA focuses on RA synovial fibroblasts (RA-SF) and their role in cartilage destruction. The model has provided the best evidence that RA-SF contribute significantly to matrix degradation, even in the absence of human lymphocytes and macrophages, since highly purified RA-SF invade the co-implanted normal human cartilage. Moreover, it became clear that they maintained their aggressive phenotype over long periods of time, particularly at sites of invasion into the co-implanted human cartilage. Targeting different signaling molecules, cytokines and matrix-degrading enzymes by soluble receptors, antagonists or negative mutants in the SCID Mouse model of RA has implicated many of them in the mechanisms leading to cartilage destruction. However, since inhibition of a single molecule or pathway is not sufficient to inhibit the aggressive behavior of RA-SF it appears necessary to co-express in the synoviocytes genes for two or even more antagonists of e.g. cytokines, matrix-degrading enzymes or molecules interfering specifically with signaling pathways involved in the apoptosis of RA-SF. Based on the recent observation that the L1 (line-1) endogenous retroviral element appears responsible for the cytokine- independent activation via the MAPK p38delta, the current understanding of disease pathogenesis suggests that both the cytokine-dependent as well as the cytokine-independent pathways of joint destruction must be inhibited. Modulation of both pathways by gene transfer approaches in the SCID Mouse model is a feasible method aimed at identifying novel targets for the prevention of cartilage destruction in RA.
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“Inverse wrap”: an improved implantation technique for virus-transduced synovial fibroblasts in the SCID Mouse model for rheumatoid arthritis
Modern rheumatology, 2001Co-Authors: Martin Judex, Thomas Pap, Elena Neumann, Martin Fleck, John D. Mountz, Jürgen Schölmerich, Kusuki Nishioka, Ulf Müller-ladnerAbstract:Abstract The SCID Mouse model for rheumatoid arthritis (RA) is an established and reliable approach to examining the distinct mechanisms operative in RA synovium, and evaluating novel gene therapy strategies. However, serum concentrations of circulating gene therapy products following gene transfer are frequently too low to allow detection. This problem stimulated us to develop a novel implantation technique to improve the yield of these soluble gene products. Synovial fibroblasts from patients with RA were cultured, passaged, and transduced with Ad5 sTNFRp55:Ig. sTNFRp55:Ig production was confirmed by ELISA, and then cells were implanted into SCID mice using a novel implantation strategy in which pieces of human cartilage were engrafted into a fibroblast-saturated inert sponge. Thereafter, the sponges were implanted under the skin of the mice instead of under the kidney capsule, as in the original approach, allowing co-implantation of larger pieces of cartilage together with higher numbers of adenovirus-transduced RA synovial fibroblasts. The improved implantation technique not only resulted in a reduction in the number of mice needed in each experiment by approximately 60%, and a reduction of the time taken for surgery by about 50%, but also considerably enhanced the serum concentrations of the gene product sTNFRp55-Ig, allowing detection of the soluble TNF receptor p55 by standard ELISA. In summary, the improved implantation technique for the SCID Mouse model for RA results in more economic animal treatment, and facilitates the detection and quantification of circulating gene products following adenovirus-based gene transfer into synovial fibroblasts.
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Gene transfer of cytokine inhibitors into human synovial fibroblasts in the SCID Mouse model.
Arthritis and rheumatism, 1999Co-Authors: Ulf Müller-ladner, Christopher P. Evans, Barry N. Franklin, Charles R. Roberts, Paul D. RobbinsAbstract:Objective To investigate the effects of retrovirus-based gene delivery of inhibitory cytokines and cytokine inhibitors into human synovial fibroblasts in the SCID Mouse model of rheumatoid arthritis (RA). Methods The MFG vector was used for gene delivery of tumor necrosis factor α receptor (TNFαR) p55, viral interleukin-10 (IL-10), and murine IL-10 into RA synovial fibroblasts. The effect on invasion of these cells into human articular cartilage and on perichondrocytic cartilage degradation was examined after 60 days of coimplantation into the SCID Mouse. Results TNFαR p55 gene transfer showed only a limited effect on inhibition of RA synovial fibroblast invasiveness and cartilage degradation. In contrast, invasion of the RA synovial fibroblasts into the coimplanted cartilage was strongly inhibited by both viral and murine IL-10. Perichondrocytic cartilage degradation was not affected by either form of IL-10. Conclusion The data show that cytokines can be successfully inserted into the genome of human RA synovial fibroblasts using a retroviral vector delivery system, and that the SCID Mouse model of human RA is a valuable tool for examining the effects of gene transfer. In addition, inhibition of more than one cytokine pathway may be required to inhibit both synovial- and chondrocyte-mediated cartilage destruction in RA.
Mike Reichelt - One of the best experts on this subject based on the ideXlab platform.
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Varicella-Zoster Virus Neurotropism in SCID Mouse–Human Dorsal Root Ganglia Xenografts
Current Topics in Microbiology and Immunology, 2010Co-Authors: Leigh Zerboni, Mike Reichelt, Ann M. ArvinAbstract:Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus and the causative agent of varicella and herpes zoster. VZV reactivation from latency in sensory nerve ganglia is a direct consequence of VZV neurotropism. Investigation of VZV neuropathogenesis by infection of human dorsal root ganglion xenografts in immunocompromised (SCID) mice has provided a novel system in which to examine VZV neurotropism. Experimental infection with recombinant VZV mutants with targeted deletions or mutations of specific genes or regulatory elements provides an opportunity to assess gene candidates that may mediate neurotropism and neurovirulence. The SCID Mouse–human DRG xenograft model may aid in the development of clinical strategies in the management of herpes zoster as well as in the development of “second generation” neuroattenuated vaccines.
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varicella zoster virus neurotropism in SCID Mouse human dorsal root ganglia xenografts
Current Topics in Microbiology and Immunology, 2010Co-Authors: Leigh Zerboni, Mike Reichelt, Ann M. ArvinAbstract:Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus and the causative agent of varicella and herpes zoster. VZV reactivation from latency in sensory nerve ganglia is a direct consequence of VZV neurotropism. Investigation of VZV neuropathogenesis by infection of human dorsal root ganglion xenografts in immunocompromised (SCID) mice has provided a novel system in which to examine VZV neurotropism. Experimental infection with recombinant VZV mutants with targeted deletions or mutations of specific genes or regulatory elements provides an opportunity to assess gene candidates that may mediate neurotropism and neurovirulence. The SCID Mouse–human DRG xenograft model may aid in the development of clinical strategies in the management of herpes zoster as well as in the development of “second generation” neuroattenuated vaccines.
Horace M. Delisser - One of the best experts on this subject based on the ideXlab platform.
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c7E3 Fab inhibits human tumor angiogenesis in a SCID Mouse human skin xenograft model
Angiogenesis, 2006Co-Authors: Marian T. Nakada, Patricia M. Sassoli, Horace M. DelisserAbstract:The αvβ3 integrin plays an important role in tumor growth and angiogenesis. Inhibition of this receptor by intact bivalent antibodies has been shown to inhibit angiogenesis and tumor growth. In this study we tested the chimeric Fab of 7E3 (c7E3 Fab), an antibody reactive with human platelet GPIIb/IIIa and αvβ3 to determine if it would inhibit in vivo angiogenesis and tumor growth in a SCID Mouse/human skin tumor growth and angiogenesis model. c7E3 Fab inhibited human tumor angiogenesis and tumor growth. These data suggest monovalent antibody fragments devoid of antibody effector function can have efficacy in preclinical models of angiogenesis.
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c7E3 Fab inhibits human tumor angiogenesis in a SCID Mouse human skin xenograft model
Angiogenesis, 2006Co-Authors: Marian T. Nakada, Patricia M. Sassoli, Gaoyuan Cao, Horace M. DelisserAbstract:The αvβ3 integrin plays an important role in tumor growth and angiogenesis. Inhibition of this receptor by intact bivalent antibodies has been shown to inhibit angiogenesis and tumor growth. In this study we tested the chimeric Fab of 7E3 (c7E3 Fab), an antibody reactive with human platelet GPIIb/IIIa and αvβ3 to determine if it would inhibit in vivo angiogenesis and tumor growth in a SCID Mouse/human skin tumor growth and angiogenesis model. c7E3 Fab inhibited human tumor angiogenesis and tumor growth. These data suggest monovalent antibody fragments devoid of antibody effector function can have efficacy in preclinical models of angiogenesis.
