Stem Cells Derived from Neonatal Mouse Kidney Generate Functional Proximal Tubule-Like Cells and Integrate into Developing Nephrons In Vitro

We have recently shown that kidney-derived stem cells (KSCs) isolated from the mouse newborn kidney differentiate into a range of kidney-specific cell types. However, the functionality and integration capacity of these mouse KSCs remain unknown. Therefore, the main objectives of this study were (1) to determine if proximal tubule-like cells, generated in vitro from KSCs, displayed absorptive function typical of proximal tubule cells in vivo, and (2) to establish whether the ability of KSCs to integrate into developing nephrons was comparable with that of metanephric mesenchyme (MM), a transient population of progenitor cells that gives rise to the nephrons during kidney organogenesis. We found that proximal tubule-like cells generated in vitro from mouse KSCs displayed megalin-dependent absorptive function. Subsequently, we used a chimeric kidney rudiment culture system to show that the KSCs could generate proximal tubule cells and podocytes that were appropriately located within the developing nephrons. Finally, we compared the ability of KSCs to integrate into developing kidneys ex vivo with that of metanephric mesenchyme cells. We found that KSCs integrated into nascent nephrons to a similar extent as metanephric mesenchyme cells while both were excluded from ureteric bud branches. Our analysis of the behavior of the two cell types shows that some, but not all KSC characteristics are similar to those of the MM

Entre artistas y restauradorӕs. Nuevos formatos de interacción e intercambio de conocimiento

Este proyecto ha tenido como objetivo la consolidación de una red de cooperación horizontal e intercambio interdisciplinar, internivelar, interdepartamental e interfacultativa entre artistas y conservadoræs-restauradoræs, así como la exploración de nuevas formas de interacción para generar conocimiento. Esta red conecta entre sí a los departamentos de la Facultad de Bellas Artes de la UCM (Dibujo y Grabado; Diseño e Imagen; y Pintura y Conservación-Restauración), al tiempo que fomenta interacciones con estudiantes y docentes de departamentos de arte y conservación-restauración de otras universidades públicas y privadas como son la Universidad de la Laguna, la Universidad Politécnica de Madrid, la Universidad Francisco de Vitoria y la Universidad Antonio Nebrija. Así mismo, incorpora a la red un organismo externo al ámbito de la universidad y vinculado al ámbito profesional de la práctica artística, como es la Asociación Cultural Atelier Solar. El proyecto ha abarcado la realización de tres encuentros, un curso, una mesa redonda, la dirección de TFGs, la visita a estudios de artistas y el desarrollo de una investigación en torno a nuevos formatos de interacción entre conservadoræs-restauradoræs y artistas. Esta memoria recoge los objetivos propuestos y evalúa los alcanzados en base a una serie de indicadores, describe la metodología utilizada en el proyecto, analiza las características del equipo de trabajo y expone las actividades desarrolladas durante el curso 2021-2022. Los Anexos incluyen documentación sobre las actividades desarrolladas e imágenes sobre los procesos de investigación

Isolation and characterization of a novel population of potential kidney stem cells from postnatal mouse kidney

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Increasing cutaneous afferent feedback improves proprioceptive accuracy at the knee in patients with sensory ataxia

Hereditary sensory and autonomic neuropathy type III features disturbed proprioception and a marked ataxic gait. We recently showed that joint-angle matching error at the knee is positively correlated with the degree of ataxia. Using intraneural microelectrodes, we also documented that these patients lack functional muscle spindle afferents but have preserved large-diameter cutaneous afferents, suggesting that patients with better proprioception may be relying more on proprioceptive cues provided by tactile afferents. We tested the hypothesis that enhancing cutaneous sensory feedback by stretching the skin at the knee joint using unidirectional elasticity tape could improve proprioceptive accuracy in patients with a congenital absence of functional muscle spindles. Passive joint angle matching at the knee was used to assess proprioceptive accuracy in 25 patients with HSAN III and 9 age-matched control subjects, with and without taping. Angles of the reference and indicator knees were recorded with digital inclinometers, and the absolute error, gradient and correlation coefficient between the two sides calculated. Patients with HSAN III performed poorly on the joint angle-matching test (mean matching error ± SE 8.0 ± 0.8°, controls 3.0 ± 0.3°). Following application of tape bilaterally to the knee in an X-shaped pattern, proprioceptive performance improved significantly in the patients (mean error 5.4 ± 0.7°) but not in the controls (3.0 ± 0.2°). Across patients, but not controls, significant increases in gradient and correlation coefficient were also apparent following taping. We conclude that taping improves proprioception at the knee in HSAN III, presumably via enhanced sensory feedback from the skin

KSC-derived proximal tubule cells display normal absorptive function.

<p>(<b>A</b>) Immunofluorescence staining shows that some KSC-derived cells expressed the proximal tubule marker megalin (green). Nuclei are stained with DAPI (blue). (<b>B</b>) Immunostaining shows that FBSA (red) was uptaken by megalin⁺ KSCs (green); nuclei are stained with DAPI (blue). Asterisks indicate cells co-stained for megalin and FBSA. (<b>C</b>) <i>In vitro</i> functionality assay demonstrates that in the presence of either receptor-associated protein (RAP), or an excess of unlabeled BSA, the uptake of FBSA (red) was almost completely blocked. Nuclei are stained with Hoechst 33342 (blue). Scale bars are 50 µm (A), 25 µm (B) and 100 µm (C).</p

Population growth of cultured MM.

<p>Growth curve of MM cells cultured in the presence of Bmp7 and Fgf2 for the following times: days 1–4 (P1, black), days 5–8 (P2, blue), days 9–12 (P3, red). The MM cell population expanded by >12-fold during the P1 and P2 culture periods, but ceased expanding during P3. Data are expressed as mean ± SD; n = 6 for P1 and P2; n = 5 for P3.</p