Harnessing mechanobiology for kidney organoid research

Recently, organoids have emerged as revolutionizing tools with the unprecedented potential to recreate organ-specific microanatomy in vitro. Upon their derivation from human pluripotent stem cells (hPSCs), organoids reveal the blueprints of human organogenesis, further allowing the faithful recapitulation of their physiology. Nevertheless, along with the evolution of this field, advanced research exposed the organoids’ shortcomings, particularly regarding poor reproducibility rates and overall immatureness. To resolve these challenges, many studies have started to underscore the relevance of mechanical cues as a relevant source to induce and externally control hPSCs differentiation. Indeed, established organoid generation protocols from hPSCs have mainly relyed on the biochemical induction of fundamental signalling pathways present during kidney formation in mammals, whereas mechanical cues have largely been unexplored. This review aims to discuss the pertinence of (bio) physical cues within hPSCs-derived organoid cultures, while deciphering their effect on morphogenesis. Moreover, we will explore state-of-the-art mechanobiology techniques as revolutionizing means for understanding the underlying role of mechanical forces in biological processes in organoid model systems

Research on Skeletal Muscle Diseases Using Pluripotent Stem Cells

The generation of induced pluripotent stem cells (iPSCs), especially the generation of patient-derived pluripotent stem cells (PSCs) suitable for disease modelling in vitro, opens the door for the potential translation of stem-cell related studies into the clinic. Successful replacement, or augmentation, of the function of damaged cells by patient-derived differentiated stem cells would provide a novel cell-based therapy for skeletal muscle-related diseases. Since iPSCs resemble human embryonic stem cells (hESCs) in their ability to generate cells of the three germ layers, patient-specific iPSCs offer definitive solutions for the ethical and histo-incompatibility issues related to hESCs. Indeed human iPSC (hiPSC)-based autologous transplantation is heralded as the future of regenerative medicine. Interestingly, during the last years intense research has been published on disease-specific hiPSCs derivation and differentiation into relevant tissues/organs providing a unique scenario for modelling disease progression, to screen patient-specific drugs and enabling immunosupression-free cell replacement therapies. Here, we revise the most relevant findings in skeletal muscle differentiation using mouse and human PSCs. Finally and in an effort to bring iPSC technology to the daily routine of the laboratory, we provide two different protocols for the generation of patient-derived iPSCs

Active superelasticity in three-dimensional epithelia of controlled shape

Fundamental biological processes are carried out by curved epithelial sheets that enclose a pressurized lumen. How these sheets develop and withstand three-dimensional deformations has remained unclear. Here we combine measurements of epithelial tension and shape with theoretical modelling to show that epithelial sheets are active superelastic materials. We produce arrays of epithelial domes with controlled geometry. Quantification of luminal pressure and epithelial tension reveals a tensional plateau over several-fold areal strains. These extreme strains in the tissue are accommodated by highly heterogeneous strains at a cellular level, in seeming contradiction to the measured tensional uniformity. This phenomenon is reminiscent of superelasticity, a behaviour that is generally attributed to microscopic material instabilities in metal alloys. We show that in epithelial cells this instability is triggered by a stretch-induced dilution of the actin cortex, and is rescued by the intermediate filament network. Our study reveals a type of mechanical behaviour—which we term active superelasticity—that enables epithelial sheets to sustain extreme stretching under constant tension

A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells

Altres ajuts: European Research Council (ERC); EIT Health under grant ID 20366 (R2U-Tox-Assay); IBEC Faster Future program (A por la COVID-19); European Regional Development Fund (FEDER); Gobierno de Navarra, Departamento de Desarrollo Económico y Empresarial (AGATA 0011-1411-2020-000011, DIANA 0011-1411-2017-000029); Ministerio de Economía y Competitividad (MINECO); IBEC International PhD Programme "La Caixa" Severo Ochoa fellowships (LCF/BQ/SO16/52270019); start-up funds from the College of Medicine at the University of Florida, Gainesville; T. von Zastrow Foundation; the FWF Wittgenstein award (Z 271-B19); the Austrian Academy of Sciences and the Canada 150 Research Chairs Program (F18-01336); the Canadian Institutes of Health Research COVID-19 (F20-02343, F20-02015); Swiss National Science Foundation fellowship (P400PM_194473/1); Swedish Research Council (2018-05766); the Innovative Medicines Initiative 2 Joint Undertaking (JU 101005026); Ayudas Fundación BBVA a Equipos de Investigación Científica SARS-CoV-2 y COVID-19 through the project "Identifying SARS-CoV-2-host cell interactions exploiting CRISPR-Cas9-engineered human organoids: through the development of specific therapies against COVID19"; Fundació la Marató de TV3 (201910-31 and 202125-3).It is not well understood why diabetic individuals are more prone to develop severe COVID-19. To this, we here established a human kidney organoid model promoting early hallmarks of diabetic kidney disease development. Upon SARS-CoV-2 infection, diabetic-like kidney organoids exhibited higher viral loads compared with their control counterparts. Genetic deletion of the angiotensin-converting enzyme 2 (ACE2) in kidney organoids under control or diabetic-like conditions prevented viral detection. Moreover, cells isolated from kidney biopsies from diabetic patients exhibited altered mitochondrial respiration and enhanced glycolysis, resulting in higher SARS-CoV-2 infections compared with non-diabetic cells. Conversely, the exposure of patient cells to dichloroacetate (DCA), an inhibitor of aerobic glycolysis, resulted in reduced SARS-CoV-2 infections. Our results provide insights into the identification of diabetic-induced metabolic programming in the kidney as a critical event increasing SARS-CoV-2 infection susceptibility, opening the door to the identification of new interventions in COVID-19 pathogenesis targeting energy metabolism

Dispositivos lingüísticos de acogida, aprendizaje expansivo e interculturalidad: Contribuciones para la inclusión educativa de estudiantes extranjeros

Indexación: Scopus.In the context of the progressive increase of foreigners in public schools in Chile and the recent changes in migratory patterns, the presence of students who do not master the working language of the educational system has systematically incremented in recent years. In a scenario marked by the absence of educational policies that respond to this new linguistic diversity, the purpose of our research was to understand how schools have responded to the arrival of foreign students and what educational practices they have implemented to tackle this challenge. Through a two-year school ethnography in four public schools with high enrollment of foreigners, institutional documents were analyzed and field observation, interviews and focus groups were conducted with different actors amidst the educational communities. Through an analysis of thematic content, the results reveal the implementation of ten devices to manage educational responses to foreign students. We have analyzed three of these devices with a focus on linguistics based on the tensions and contradictions that occur within the educational institutions of which they are part, identifying significant elements and dimensions to drive forward expansive learning. Finally, we discuss these findings in light of the advances and challenges of the intercultural approach in our Latin American region.https://www.scielo.br/j/ep/a/NhL67jbv7H7VpZtQYjtHVFt/?lang=e

Revista de educación

La participación en un proyecto de evaluación tiene consecuencias inmediatas para la universidad, en la medida en que sirve para concienciarse de sus problemas, de sus posibilidades y ayuda a diseñar planes internos de actuación para mejorar sus niveles de calidad y su prestigio. Por otra parte, la difusión de los resultados de la evaluación servirá también para un mejor conocimiento de cada universidad por parte del entorno social, de los niveles de calidad alcanzados por ésta y de los esfuerzos que realiza por mejorar sus prestaciones y su servicio a la sociedad. Todo ello, debe contribuir a aumentar el apoyo social a las instituciones universitarias. Por último, las Administraciones Públicas con competencias en política universitaria, podrán utilizar los resultados de los proyectos de evaluación de la calidad para diseñar sus planes de actuación en materia de desarrollo y de financiación de las universidades.Ministerio Educación CIDEBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5 - 3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

Non-coding microRNAs for cardiac regeneration: Exploring novel alternatives to induce heart healing

In recent years, different studies have revealed that adult mammalian cardiomyocytes have the capacity to self-renew under homeostatic conditions and after myocardial injury. Interestingly, data from animal models capable of regeneration, such as the adult zebrafish and neonatal mice, have identified different non-coding RNAs (ncRNAs) as functional RNA molecules driving cardiac regeneration and repair. In this review, we summarize the current knowledge of the roles that a specific subset of ncRNAs, namely microRNAs (miRNA), plays in these animal models. We also emphasize the importance of characterizing and manipulating miRNAs as a novel approach to awaken the dormant regenerative potential of the adult mammalian heart by the administration of miRNA mimics or inhibitors. Overall, the use of these strategies alone or in combination with current cardiac therapies may represent new avenues to pursue for cardiac regeneration. Keywords: Heart failure, Non-coding RNAs, miRNAs, Animal models, Regeneratio

Modeling epigenetic modifications in renal development and disease with organoids and genome editing

Understanding epigenetic mechanisms is crucial to our comprehension of gene regulation in development and disease. In the past decades, different studies have shown the role of epigenetic modifications and modifiers in renal disease, especially during its progression towards chronic and end-stage renal disease. Thus, the identification of genetic variation associated with chronic kidney disease has resulted in better clinical management of patients. Despite the importance of these findings, the translation of genotype–phenotype data into gene-based medicine in chronic kidney disease populations still lacks faithful cellular or animal models that recapitulate the key aspects of the human kidney. The latest advances in the field of stem cells have shown that it is possible to emulate kidney development and function with organoids derived from human pluripotent stem cells. These have successfully recapitulated not only kidney differentiation, but also the specific phenotypical traits related to kidney function. The combination of this methodology with CRISPR/Cas9 genome editing has already helped researchers to model different genetic kidney disorders. Nowadays, CRISPR/Cas9-based approaches also allow epigenetic modifications, and thus represent an unprecedented tool for the screening of genetic variants, epigenetic modifications or even changes in chromatin structure that are altered in renal disease. In this Review, we discuss these technical advances in kidney modeling, and offer an overview of the role of epigenetic regulation in kidney development and disease

Active superelasticity in three-dimensional epithelia of controlled shape

International audienc