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by Keyword: Divergent features
Garreta, E, Moya-Rull, D, Centeno, A, Marco, A, Ullate-Agote, A, Amato, G, Aranda, CJ, Oria, R, Lozano-Ojalvo, D, Pool, MBF, Hamelink, TL, Selfa, IL, González, F, Tarantino, C, Salinas, AM, San Martín, PL, Koshy, P, Gavaldà-Navarro, A, Vilas-Zornoza, A, Rodríguez-Madoz, JR, García, AF, Marquez-Leiva, I, Leuvenink, HGD, Belda-Iniesta, C, Naesens, M, Dominguez-Gil, B, González-Martín, M, Rodríguez-Rivera, J, Ochando, J, Prosper, F, Moers, C, Montserrat, N, (2025). Systematic production of human kidney organoids for transplantation in porcine kidneys during ex vivo machine perfusion Nature Biomedical Engineering , 
Organoids derived from human pluripotent stem (hPS) cells hold promise for therapeutic purposes. However, technological advances to overcome their massive production while ensuring differentiation fidelity are still lacking. Here we report a procedure sustaining the derivation of kidney organoids from hPS cells (hPSC-kidney organoids) using a scalable, reproducible and affordable approach that allows hPSC-kidney organoid differentiation into different renal cell types. Using single-cell RNA sequencing, confocal image analysis, metabolic assays and CRISPR-Cas9 engineering for generation of fluorescent reporters, we show that hPSC-kidney organoids exhibit transcriptional variety and cellular composition following cell-to-cell contact. We infuse human kidney organoids into ex vivo porcine kidneys using normothermic machine perfusion, and demonstrate in vivo engraftment of hPSC-kidney organoids. We further evaluate the immune response, confirming the feasibility and viability of the procedure. We identify cells of human origin after normothermic machine perfusion and in vivo transplantation by means of in situ hybridization, immunohistochemistry, confocal microscopy, image analysis and quantification, in vivo imaging, and flow cytometry. This work provides a foundation for using hPSC-kidney organoids for ex vivo cell-based therapies in clinical trials.
JTD Keywords: Divergent features, Mouse, Reveals, Static cold-storage
Garreta, E, Nauryzgaliyeva, Z, Marco, A, Safi, W, Montserrat, N, (2022). Dissecting nephron morphogenesis using kidney organoids from human pluripotent stem cells CURRENT OPINION IN GENETICS & DEVELOPMENT 72, 22-29
During kidney development the emergence of complex multicellular shapes such as the nephron (the functional unit of the kidney) rely on spatiotemporally coordinated developmental programs. These involve gene regulatory networks, signaling pathways and mechanical forces, that work in concert to shape and form the nephron(s). The generation of kidney organoids from human pluripotent stem cells now represent an unprecedented experimental set up to study these processes. Here we discuss the potential applications of kidney organoids to advance our knowledge of how mechanical forces and cell fate specification spatiotemporally interact to orchestrate nephron patterning and morphogenesis in humans. Progress in innovative techniques for quantifying and perturbing these processes in a controlled manner will be crucial. A mechanistic understanding of the multicellular dynamic processes occurring during nephrogenesis will pave the way to unveil new mechanisms of human kidney disease. © 2021
JTD Keywords: differentiation, dynamics, induction, lumen formation, models, mouse, organogenesis, reveals, tubules, Cell differentiation, Divergent features, Humans, Kidney, Morphogenesis, Nephrons, Organoids, Pluripotent stem cells
