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      13Scopus© Citations 2
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    Intravitreal administration of multipotent mesenchymal stromal cells triggers a cytoprotective microenvironment in the retina of diabetic mice
    (2016) ;
    Cristhian A. Urzua
    ;
    Scarleth Montecino
    ;
    Karla Leal
    ;
    <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Diabetic retinopathy is a common complication of diabetes and the leading cause of irreversible vision loss in the Western world. The reduction in color/contrast sensitivity due to the loss of neural cells in the ganglion cell layer of the retina is an early event in the onset of diabetic retinopathy. Multipotent mesenchymal stromal cells (MSCs) are an attractive tool for the treatment of neurodegenerative diseases, since they could differentiate into neuronal cells, produce high levels of neurotrophic factors and reduce oxidative stress. Our aim was to determine whether the intravitreal administration of adipose-derived MSCs was able to prevent the loss of retinal ganglion cells in diabetic mice.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Diabetes was induced in C57BL6 mice by the administration of streptozotocin. When retinal pro-damage mechanisms were present, animals received a single intravitreal dose of 2 × 10<jats:sup>5</jats:sup> adipose-derived MSCs or the vehicle. Four and 12 weeks later we evaluated: (a) retinal ganglion cell number (immunofluorescence); (b) neurotrophic factor levels (real-time quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA)); (c) retinal apoptotic rate (TUNEL); (d) retinal levels of reactive oxygen species and oxidative damage (ELISA); (e) electrical response of the retina (electroretinography); (f) pro-angiogenic and anti-angiogenic factor levels (RT-qPCR and ELISA); and (g) retinal blood vessels (angiography). Furthermore, 1, 4, 8 and 12 weeks post-MSC administration, the presence of donor cells in the retina and their differentiation into neural and perivascular-like cells were assessed (immunofluorescence and flow cytometry).</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>MSC administration completely prevented retinal ganglion cell loss. Donor cells remained in the vitreous cavity and did not differentiate into neural or perivascular-like cells. Nevertheless, they increased the intraocular levels of several potent neurotrophic factors (nerve growth factor, basic fibroblast growth factor and glial cell line-derived neurotrophic factor) and reduced the oxidative damage in the retina. Additionally, MSC administration has a neutral effect on the electrical response of the retina and did not result in a pathological neovascularization.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Intravitreal administration of adipose-derived MSCs triggers an effective cytoprotective microenvironment in the retina of diabetic mice. Thus, MSCs represent an interesting tool in order to prevent diabetic retinopathy.</jats:p> </jats:sec>
      1  1Scopus© Citations 119
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    Proregenerative Microenvironment Triggered by Donor Mesenchymal Stem Cells Preserves Renal Function and Structure in Mice with Severe Diabetes Mellitus
    (2015) ;
    Maximiliano Giraud-Billoud
    ;
    Daniel Carpio
    ;
    Fabián Cabezas
    ;
    <jats:p>The aim of our work was to evaluate, in an animal model of severe diabetes mellitus, the effect of mesenchymal stem cells (MSCs) administration on diabetic nephropathy (DN) progression. After diabetes induction, one group of mice received the vehicle (DM) and other group received a single dose of MSCs (DM + MSCs). DM + MSCs mice showed a significant improvement in functional parameters of the kidney compared with untreated mice. While DM mice presented marked histopathological changes characteristics of advanced stages of DN (fibrosis, glomerulosclerosis, glomerular basement membrane thickening, capillary occlusion, decreased podocyte density, and effacement of foot processes), DM + MSCs mice showed only slight tubular dilatation. The renoprotection was not associated with an improvement in diabetic condition and very low number of donor cells was found in the kidney of DM + MSCs mice, suggesting that renoprotection could be mediated by paracrine effects. Indeed, DM + MSC mice presented increased renal proliferation index, decreased renal apoptotic index and the restoration of proregenerative factors, and anti-inflammatory cytokines levels. Moreover, macrophage infiltration and oxidative stress damage were also reduced in DM + MSCs mice. Our data demonstrate that MSC administration triggers a proregenerative microenvironment in DN kidney, which allows the preservation of the renal function even if diabetes was uncorrected.</jats:p>
      1  1Scopus© Citations 59
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    Diseño y validación de un cuestionario para evaluar oportunidades de práctica pedagógica, metacognición y «lifelong learning», brindadas por los programas de formación inicial docente
    (2021)
    Kiomi Matsumoto-Royo
    ;
    MarĂ­a-Soledad RamĂ­rez-Montoya
    ;
    <jats:p>El objetivo del estudio fue diseñar y validar un cuestionario para recoger información respecto de las oportunidades que brindan los programas de formación inicial docente de aproximarse a la práctica pedagógica, de desarrollar habilidades de procesamiento metacognitivo y de adoptar el lifelong learning. El instrumento fue diseñado conforme a la literatura y validado usando el método Delphi. Fue aplicado en una muestra de 198 estudiantes de Pedagogía. Luego de ajustes en función de los resultados de un análisis factorial confirmatorio, se obtuvo una versión de alta validez y confiabilidad. El cuestionario está organizado en tres dimensiones y 24 reactivos y permite estudiar desde la perspectiva de los estudiantes las acciones de los programas de formación docente, constituyendo un marco referencial para orientar las decisiones de ajuste e innovación en este ámbito de formación.</jats:p>
      11Scopus© Citations 8
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    Feedback as an opportunity to promote lifelong learning in pre-service teachers: a mixed methods study
    (2023)
    Kiomi Matsumoto-Royo
    ;
    ;
    Maria Soledad RamĂ­rez-Montoya
    <jats:p>The aim of this study was to investigate whether, within a practice-based curriculum, feedback on the assessment tasks provided during campus coursework offers opportunities to promote lifelong learning dispositions in pre-service teachers. For this, pre-service teachers (<jats:italic>n</jats:italic> = 231) completed a validated questionnaire regarding lifelong learning dispositions. Then, feedback from assessment tasks (<jats:italic>n</jats:italic> = 14) was analyzed to identify claims related to curiosity, motivation, perseverance, and self-regulation of learning. Finally, in-depth interviews were conducted with pre-service teachers (<jats:italic>n</jats:italic> = 8) to explore their perspectives on feedback and lifelong learning dispositions. Data triangulation was used to confirm and add depth to the findings. Feedback on assessment tasks provided during campus course work promotes lifelong learning dispositions when: (i) tied to authentic tasks, (ii) is provide not only by teacher educators but also by peers, (iii) incorporates both positive and negative comments, along with practical advice. The implication of findings for teacher education is discussed.</jats:p>
    Scopus© Citations 1
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    Dexamethasone and rosiglitazone are sufficient and necessary for producing functional adipocytes from mesenchymal stem cells
    (2015) ; ;
    Maximiliano Espinosa
    ;
    Martha Arango-Rodriguez
    ;
    Carlos Puebla
    <jats:p> The final product of adipogenesis is a functional adipocyte. This mature cell acquires the necessary machinery for lipid metabolism, loses its proliferation potential, increases its insulin sensitivity, and secretes adipokines. Multipotent mesechymal stromal cells have been recognized as a source of adipocytes both in vivo and in vitro. The in vitro adipogenic differentiation of human MSC (hMSC) has been induced up to now by using a complex stimulus which includes dexamethasone, 3-isobutyl-1-methylxanthine, indomethacin, and insulin (a classical cocktail) and evaluated according to morphological changes. The present work was aimed at demonstrating that the simultaneous activation of dexamethasone’s canonical signaling pathways, through the glucocorticoid receptor and CCAAT-enhancer-binding proteins ( C/EBPs) and rosiglitazone through peroxisome proliferator-activated receptor gamma ( PPAR-gamma) is sufficient yet necessary for inducing hMSC adipogenic differentiation. It was also ascertained that hMSC exposed just to dexamethasone and rosiglitazone (D&amp;R) differentiated into cells which accumulated neutral lipid droplets, expressed C/EBP-alpha, PPAR-gamma, aP2, lipoprotein lipase, acyl-CoA synthetase, phosphoenolpyruvate carboxykinase, adiponectin, and leptin genes but did not proliferate. Glucose uptake was dose dependent on insulin stimulus and high levels of adipokines were secreted (i.e. displaying not only the morphology but also expressing mature adipocytes’ specific genes and functional characteristics). This work has demonstrated that (i) the activating C/EBPs and PPAR-gamma signaling pathways were sufficient to induce adipogenic differentiation from hMSC, (ii) D&amp;R producing functional adipocytes from hMSC, (iii) D&amp;R induce adipogenic differentiation from mammalian MSC (including those which are refractory to classical adipogenic differentiation stimuli). D&amp;R would thus seem to be a useful tool for MSC characterization, studying adipogenesis pathways and producing functional adipocytes. </jats:p>
      1  1Scopus© Citations 57
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      20Scopus© Citations 2
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      1  2Scopus© Citations 308