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Histopathological characteristics of human non-tumor thyroid tissues in a long-term model of adenomatous goiter xenografts in the NOD/Shi-scid,IL-2Rγnull mouse
Institution:1. Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas & Facultad Medicina, Universidad de Chile, Santiago, Chile;2. Centro Estudios Moleculares de la Célula (CEMC), Facultad de Ciencias Químicas y Farmacéuticas & Facultad Medicina, Universidad de Chile, Santiago, Chile;3. Departamento de Química Inorgánica y Analítica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile;4. Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile;5. Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden;6. Cardiovascular and Metabolic Diseases iMed, AstraZeneca R&D, 43183 Mölndal, Sweden;7. The Hatter Cardiovascular Institute, University College London, London, UK;8. Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile;9. Department of Internal Medicine/Cardiology Division, University of Texas Southwestern Medical Center, Dallas, TX, USA
Abstract:There is a growing need for modeling the human thyroid to link data obtained from animals to humans because of its sensitivity to radiation exposure and endocrine disruption chemicals. In a scid mouse model produced by transplanting human thyroid tissues, leakiness and thymic lymphoma that occurs spontaneously in the scid mouse can complicate the interpretation of experimental results. Considering that the NOD.Cg-Prkdcscid Il2rgtm1Sug/Jic mouse (NOD/Shi-scid, IL-2Rγnull or NOG mouse) may be a better host because this strain has low incidence of leakiness and thymic lymphoma, we have evaluated the potential of a model that allows long-term observation of non-tumor human thyroid tissues in this mouse. We transplanted tissues of human adenomatous goiter into NOG mice and examined the tissues histopathologically. The morphology of human adenomatous goiter tissues was maintained from 24 to 44 weeks after transplantation in NOG mice with no noted differences between donor-matched tissues or the weeks after transplantation. The tissues expressed thyroglobulin protein and mRNA as well as thyroperoxidase. Endothelial cells originating from human were found in the transplanted tissues and were thought to be a characteristic of this model. The intactness of the tissues before transplantation was found to affect the rate of tissue engraftment. From the present results we have concluded that transplanted thyroid tissues in NOG mice maintain the histopathological characteristics of their origin for long terms. Therefore this model was thought feasible for toxicity evaluation.
Keywords:NOG mouse  Transplantation  Human thyroid  Adenomatous goiter  Leakiness  Thymic lymphoma
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