Browsing by Subject "Animal models"

Now showing 1 - 4 of 4
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    Advances in translational orthopaedic research with species-specific multipotent mesenchymal stromal cells derived from the umbilical cord
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2021) Ramallo, Melina; Carreras Sánchez, Irene; López Fernández, Alba; Vélez, Roberto; Aguirre, Màrius; Feldman, Sara; Vives, Joaquim
    Compliance with current regulations for the development of innovative medicines require the testing of candidate therapies in relevant translational animal models prior to human use. This poses a great challenge when the drug is composed of cells, not only because of the living nature of the active ingredient but also due to its human origin, which can subsequently lead to a xenogeneic response in the animals. Although immunosuppression is a plausible solution, this is not suitable for large animals and may also influence the results of the study by altering mechanisms of action that are, in fact, poorly understood. For this reason, a number of procedures have been developed to isolate homologous species-specific cell types to address preclinical pharmacodynamics, pharmacokinetics and toxicology. In this work, we present and discuss advances in the methodologies for derivation of multipotent Mesenchymal Stromal Cells derived from the umbilical cord, in general, and Wharton’s jelly, in particular, from medium to large animals of interest in orthopaedics research, as well as current and potential applications in studies addressing proof of concept and preclinical regulatory aspects.
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    Biomechanical and histological analyses of a multilayer stent in a swine model of suprarenal aortic aneurysm
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Tobita, Allana Maryel; Strazzi, Anna Paula Weinhardt Baptista; Portugal, Maria Fernanda Cassino; Wolosker, Nelson; Aun, Ricardo; Monteiro, Frederico de Lima Jacy; Vieira da Silva, Luiz; Sincos, Igor Rafael; Biología Celular e Histología
    Objectives. To analyze and compare, in an animal model, the treatment of thoracoabdominal aneurysms with multilayer stents and its hemodynamic effects through the biomechanical and histological analysis of the aortic wall in contact with the stent. Methods. Large White pigs were randomized into two groups: Stent (n=6) and Control (n=5, non-stent). All animals were subjected to the creation of a suprarenal aneurysm with a bovine pericardial patch. In the Stent group, a multilayer stent was implanted immediately after aneurysm formation. After four weeks, all animals were subjected to angiographic assessment and intravascular ultrasound, and the stent was explanted before euthanasia for histological and biomechanical analyses. Results. At histological analysis, the groups did not differ significantly in maximum thickness of the intima (p=0.526), media (p=0.129), or adventitia (p=0.662). Thrombus formation was observed in 100% of the animals on the intima and media layers of the stented aorta vs. none in the Control group (p=0.048). At biomechanical analysis, no statistical differences were observed in aortic wall elasticity (p=0.158), strength (p=0.360), or thickness (p=0.323). Conclusion. We identified thrombosis of the aneurysmal sac through the presence of thrombi on the intima of the aorta in 100% of the animals in the Stent group; as for the biomechanical analysis, this study showed no statistical differences in vessel wall thickness, strength, and elasticity between
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    The tick-derived rBmTI-A protease inhibitor attenuates the histological and functional changes induced by cigarette smoke exposure
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Lourenço, Juliana D.; Ito, Juliana T.; Cervilha, Daniela A.B.; Sales, Davi S.; Riani, Alyne; Suehiro, Camila L.; Genaro, Isabella S.; Duran, Adriana; Puzer, Luciano; Martins, Milton A.; Sasaki, Sérgio D.; Lopes, Fernanda D.T.Q.S.
    Introduction. Smoking is the main risk factor for chronic obstructive pulmonary disease development and cigarette smoke (CS) exposure is considered an important approach to reproduce in rodents this human disease. We have previously shown that in an elastase-induced model of emphysema, the administration of a protease inhibitor (rBmTI-A) prevented and attenuated tissue destruction in mice. Thus, in this study we aimed to verify the effects of rBmTI-A administration on the physiopathological mechanisms of CS-induced emphysema. Methods. Mice (C57BL/6) were exposed to CS or room air for 12 weeks. In this period, 3 nasal instillations of rBmTI-A inhibitor or its vehicle were performed. After euthanasia, respiratory mechanics were evaluated and lungs removed for analysis of mean linear intercept, volume proportion of collagen and elastic fibers, density of polymorphonuclear cells, macrophages, and density of positive cells for MMP-12, MMP-9, TIMP-1 and gp91phox. Results. The rBmTI-A administration improved tissue elastance, decreased alveolar enlargement and collagen fibers accumulation to control levels and attenuated elastic fibers accumulation in animals exposed to CS. There was an increase of MMP12, MMP-9 and macrophages in CS groups and the rBmTIA only decreased the number of MMP-12 positive cells. Also, we demonstrated an increase in gp91phox in CS treated group and in TIMP-1 levels in both rBmTI-A treated groups. Conclusion. In summary, the rBmTI-A administration attenuated emphysema development by an increase of gp91phox and TIMP-1, accompanied by a decrease in MMP-12 levels.
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    Visual deficits and diagnostic and therapeutic strategies for neurofibromatosis type 1: bridging science and patient-centered care
    (MDPI, 2024-05-09) Miyagishima, Kiyoharu J.; Qiao, Fengyu; Stasheff, Steven F.; Nadal-Nicolás, Francisco Manuel; Oftalmología, Optometría, Otorrinolaringología y Anatomía Patológica; Facultad de Óptica y Optometría
    Neurofibromatosis type 1 (NF1) is an inherited autosomal dominant disorder primarily affecting children and adolescents characterized by multisystemic clinical manifestations. Mutations in neurofibromin, the protein encoded by the Nf1 tumor suppressor gene, result in dysregulation of the RAS/MAPK pathway leading to uncontrolled cell growth and migration. Neurofibromin is highly expressed in several cell lineages including melanocytes, glial cells, neurons, and Schwann cells. Individuals with NF1 possess a genetic predisposition to central nervous system neoplasms, particularly gliomas affecting the visual pathway, known as optic pathway gliomas (OPGs). While OPGs are typically asymptomatic and benign, they can induce visual impairment in some patients. This review provides insight into the spectrum and visual outcomes of NF1, current diagnostic techniques and therapeutic interventions, and explores the influence of NF1-OPGS on visual abnormalities. We focus on recent advancements in preclinical animal models to elucidate the underlying mechanisms of NF1 pathology and therapies targeting NF1-OPGs. Overall, our review highlights the involvement of retinal ganglion cell dysfunction and degeneration in NF1 disease, and the need for further research to transform scientific laboratory discoveries to improved patient outcomes.