To assess the safety of and protection conferred by Nissle, researchers modeled infection in stem cell-derived human intestinal organoids.
[American Society for Microbiology]
Using ex vivo and in vivo models of metastasis, scientists established that keratin-14+ breast cancer cells were vulnerable to natural killer cells.
[Journal of Cell Biology]
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Chan, I. S., Knútsdóttir, H., Ramakrishnan, G., Padmanaban, V., Warrier, M., Ramirez, J. C., Dunworth, M., Zhang, H., Jaffee, E. M., Bader, J. S., & Ewald, A. J. (2020). Cancer cells educate natural killer cells to a metastasis-promoting cell state. Journal of Cell Biology, 219(9). https://doi.org/10.1083/jcb.202001134 Cite
The authors discuss the applications, advantages and disadvantages of human organoids as models of development and disease and outlines the challenges that have to be overcome for organoids to be able to substantially reduce the need for animal experiments.
[Nature Reviews Molecular Cell Biology]
To investigate the pathogenetic mechanisms of mitochondrial presequence processing, researchers employed cortical neurons and cerebral organoids generated from PITRM1-knockout human iPSCs.
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Pérez, M. J., Ivanyuk, D., Panagiotakopoulou, V., Di Napoli, G., Kalb, S., Brunetti, D., Al-Shaana, R., Kaeser, S. A., Fraschka, S. A.-K., Jucker, M., Zeviani, M., Viscomi, C., & Deleidi, M. (2020). Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer’s disease-like pathology in human cerebral organoids. Molecular Psychiatry, 1–18. https://doi.org/10.1038/s41380-020-0807-4 Cite
Scientists demonstrated that post-ionizing radiation (IR) overexpression of TIGAR, a critical downstream target of c-MYC in mouse intestine, mounted a hyperplastic response in Bmi1-creERT+ reserve intestinal stem cells, and thus rescued mice from lethal IR exposure.
[Cell Death & Disease]
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Chen, F., Zhang, Y., Hu, S., Shi, X., Wang, Z., Deng, Z., Lin, L., Zhang, J., Pan, Y., Bai, Y., Liu, F., Zhang, H., & Shao, C. (2020). TIGAR/AP-1 axis accelerates the division of Lgr5 − reserve intestinal stem cells to reestablish intestinal architecture after lethal radiation. Cell Death & Disease, 11(7), 1–12. https://doi.org/10.1038/s41419-020-2715-6 Cite
Barrett’s esophagus patient biopsies and murine Barrett’s esophagus organoids were cultured ex vivo in the presence of a caspase-1 inhibitor, to determine the importance of caspase-1 for inflammatory cytokine and chemokine secretion.
[Cancer Immunology Immunotherapy]
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Barber, G., Anand, A., Katarzyna Oficjalska, Phelan, J. J., Heeran, A. B., Flis, E., Clarke, N. E., Watson, J. A., Strangmann, J., Flood, B., O’Neill, H., O’Toole, D., MacCarthy, F., Ravi, N., Reynolds, J. V., Kay, E. W., Quante, M., O’Sullivan, J., & Creagh, E. M. (2020). Characterizing caspase-1 involvement during esophageal disease progression. Cancer Immunology, Immunotherapy. https://doi.org/10.1007/s00262-020-02650-4 Cite
Mice ileum organoids were used to evaluate the long‐term effects of grape‐seed proanthocyanidin extract and two of its main components, epicatechin and gallic acid, on intestinal differentiation.
[Molecular Nutrition & Food Research]
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Scientists demonstrated that GBM associated gene regulatory modules were characterized by diagnostic quiescent stem cell marker genes.
Researchers investigated the transcriptomes of jejunum organoids derived from the same pig as well as batch-to-batch variation of organoids derived from different pigs over long-term passage.
[Frontiers in Cell and Developmental Biology]
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Investigators tested conditioned media of individual patient-derived organoids (PDOs) for cell-free tumor DNA to detect driver mutations already early on during the expansion process in order to accelerate the genetic characterization of PDOs as well as subsequent functional testing.
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Dantes, Z., Yen, H.-Y., Pfarr, N., Winter, C., Steiger, K., Muckenhuber, A., Hennig, A., Lange, S., Engleitner, T., Öllinger, R., Maresch, R., Orben, F., Heid, I., Kaissis, G. A., Shi, K., Topping, G. J., Stögbauer, F., Wirth, M., Peschke, K., … Reichert, M. (2020). Implementing cell-free DNA of pancreatic cancer patient-derived organoids for personalized oncology. JCI Insight. https://doi.org/10.1172/jci.insight.137809 Cite
In human small intestinal organoids, enterocytes were readily infected by SARS-CoV and SARS-CoV-2, as demonstrated by confocal and electron microscopy.
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Lamers, M. M., Beumer, J., Vaart, J. van der, Knoops, K., Puschhof, J., Breugem, T. I., Ravelli, R. B. G., Schayck, J. P. van, Mykytyn, A. Z., Duimel, H. Q., Donselaar, E. van, Riesebosch, S., Kuijpers, H. J. H., Schipper, D., Wetering, W. J. van de, Graaf, M. de, Koopmans, M., Cuppen, E., Peters, P. J., … Clevers, H. (2020). SARS-CoV-2 productively infects human gut enterocytes. Science, 369(6499), 50–54. https://doi.org/10.1126/science.abc1669 Cite