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      Swine as Models in Biomedical Research and Toxicology Testing

      1 , 2 , 3 , 4 , 5
      Veterinary Pathology
      SAGE Publications

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          Abstract

          Swine are considered to be one of the major animal species used in translational research, surgical models, and procedural training and are increasingly being used as an alternative to the dog or monkey as the choice of nonrodent species in preclinical toxicologic testing of pharmaceuticals. There are unique advantages to the use of swine in this setting given that they share with humans similar anatomic and physiologic characteristics involving the cardiovascular, urinary, integumentary, and digestive systems. However, the investigator needs to be familiar with important anatomic, histopathologic, and clinicopathologic features of the laboratory pig and minipig in order to put background lesions or xenobiotically induced toxicologic changes in their proper perspective and also needs to consider specific anatomic differences when using the pig as a surgical model. Ethical considerations, as well as the existence of significant amounts of background data, from a regulatory perspective, provide further support for the use of this species in experimental or pharmaceutical research studies. It is likely that pigs and minipigs will become an increasingly important animal model for research and pharmaceutical development applications.

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          Most cited references33

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          The use of pigs in neuroscience: modeling brain disorders.

          The use of pigs in neuroscience research has increased in the past decade, which has seen broader recognition of the potential of pigs as an animal for experimental modeling of human brain disorders. The volume of available background data concerning pig brain anatomy and neurochemistry has increased considerably in recent years. The pig brain, which is gyrencephalic, resembles the human brain more in anatomy, growth and development than do the brains of commonly used small laboratory animals. The size of the pig brain permits the identification of cortical and subcortical structures by imaging techniques. Furthermore, the pig is an increasingly popular laboratory animal for transgenic manipulations of neural genes. The present paper focuses on evaluating the potential for modeling symptoms, phenomena or constructs of human brain diseases in pigs, the neuropsychiatric disorders in particular. Important practical and ethical aspects of the use of pigs as an experimental animal as pertaining to relevant in vivo experimental brain techniques are reviewed. Finally, current knowledge of aspects of behavioral processes including learning and memory are reviewed so as to complete the summary of the status of pigs as a species suitable for experimental models of diverse human brain disorders.
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            Immunopathology of hyperacute xenograft rejection in a swine-to-primate model.

            Hyperacute rejection is the inevitable consequence of the transplantation of vascularized organs between phylogenetically distant species. The nature of the incompatibility and the pathogenetic mechanisms that lead to hyperacute xenograft rejection are incompletely understood. We investigated these issues by the immunopathological analysis of tissues from swine renal and cardiac xenografts placed in rhesus monkeys. Hyperacute rejection was associated with deposition of recipient IgM and classic but not alternative complement pathway components along endothelial surfaces, the formation of platelet and fibrin thrombi, and the infiltration of neutrophils. In animals from which natural antibody was temporarily depleted by organ perfusion, rejection was observed at 3 days to 5 days posttransplant. The immunopathology of rejection in these tissues revealed focal vascular changes similar to those observed in hyperacute rejection. A xenograft functioning for a prolonged period in a recipient temporarily depleted of circulating natural antibody contained recipient IgM along endothelial surfaces but no evidence for significant deposition of complement, formation of platelet and fibrin thrombi, or infiltration of neutrophils. These results suggest that rhesus IgM contributes significantly to the development of hyperacute rejection in the swine to Rhesus model and that the fixation of complement is a critical factor in the recruitment of the coagulation cascade and platelet aggregation--and possibly in the adherence and infiltration of PMN.
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              The pig as a potential xenograft donor.

              Miniature swine have several advantages over other potential donor species as a xenograft donor for clinical use. Among these advantages are: (1) unlimited availability; (2) size (similar to human beings); (3) breeding characteristics; (4) physiologic and immunologic similarities to humans. Because of the genetic disparity between these two species, routine immunosuppression will probably not suffice for the long-term survival of pig to primate xenografts. Studies are therefore underway to induce tolerance across this species barrier, utilizing a mixed chimerism approach which has previously been successful for allogeneic and concordant xenogeneic combinations. Hyperacute rejection has been eliminated by an absorption technique and pig kidney xenograft survivals up to 13 days have been achieved.
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                Author and article information

                Journal
                Veterinary Pathology
                Vet Pathol
                SAGE Publications
                0300-9858
                1544-2217
                January 13 2011
                March 2012
                March 25 2011
                March 2012
                : 49
                : 2
                : 344-356
                Affiliations
                [1 ]Medical University of South Carolina, Charleston, SC
                [2 ]LAB Research, Copenhagen, Denmark
                [3 ]Center for Comparative Medicine and Department of Pathology & Immunology Baylor College of Medicine, Houston, TX
                [4 ]Texas A&M University, College of Veterinary Medicine, College Station, TX
                [5 ]GlaxoSmithKline, King of Prussia, PA
                Article
                10.1177/0300985811402846
                21441112
                a3ce5ccf-f39e-4be0-97a1-064decf07ce4
                © 2012

                http://journals.sagepub.com/page/policies/text-and-data-mining-license

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