In vitro organoids generated from epithelial cells of mouse or patient with idiopathic pulmonary fibrosis co-cultured with young, aged or retinoic acid-pretreated murine fibroblasts were used to test potential targets.
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Gokey, J. J., Snowball, J., Green, J., Waltamath, M., Spinney, J. J., Black, K. E., Hariri, L. P., Xu, Y., & Perl, A. K. (2021). Pretreatment of aged mice with retinoic acid supports alveolar regeneration via upregulation of reciprocal PDGFA signalling. Thorax. https://doi.org/10.1136/thoraxjnl-2020-214986 Cite
The authors discuss the enhancement of organoid systems for therapeutic applications using biofabrication and organoid-on-chip platforms, which facilitate the assembly of complex organoid systems for in vitro modeling of development and diseases.
Scientists found that recombinant EREG, BTC, and NRG1 but not Lgr5 ligand R-Spondin promoted growth and proliferation of Apc double mutant colonic organoids.
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Westendorp, F., Karpus, O. N., Koelink, P. J., Vermeulen, J. L. M., Meisner, S., Koster, J., Büller, N. V. J. A., Wildenberg, M. E., Muncan, V., & van den Brink, G. R. (2021). Epithelium-derived Indian Hedgehog restricts stromal expression of ErbB family members that drive colonic tumor cell proliferation. Oncogene, 1–16. https://doi.org/10.1038/s41388-020-01633-0 Cite
Researchers found that the expression levels of several genes, which were highly expressed in original colorectal carcinoma tissues, were downregulated in organoids but re-expressed in organoids by co-culturing with cancer-associated fibroblasts.
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Naruse, M., Ochiai, M., Sekine, S., Taniguchi, H., Yoshida, T., Ichikawa, H., Sakamoto, H., Kubo, T., Matsumoto, K., Ochiai, A., & Imai, T. (2021). Re-expression of REG family and DUOX s genes in CRC organoids by co-culturing with CAFs. Scientific Reports, 11(1), 2077. https://doi.org/10.1038/s41598-021-81475-2 Cite
To fast-track translation of therapies and to inform personalised medicine, researchers aimed to develop a whole-tissue ex vivo explant model that maintains viability, 3D multicellular architecture, and microenvironmental cues of human pancreatic tumours.
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Kokkinos, J., Sharbeen, G., Haghighi, K. S., Ignacio, R. M. C., Kopecky, C., Gonzales-Aloy, E., Youkhana, J., Timpson, P., Pereira, B. A., Ritchie, S., Pandzic, E., Boyer, C., Davis, T. P., Butler, L. M., Goldstein, D., McCarroll, J. A., & Phillips, P. A. (2021). Ex vivo culture of intact human patient derived pancreatic tumour tissue. Scientific Reports, 11(1), 1944. https://doi.org/10.1038/s41598-021-81299-0 Cite
Scientists review recent advances in the development of CNS organoid models, their application in neurodegenerative diseases and technical limitations.
[Tissue Engineering Part C: Methods]
Scientists purified different cochlear cell types from neonatal mice, validated the composition of the different groups with single-cell RNA sequencing, and assessed the various groups’ potential to grow into inner ear organoids.
The authors detail recent advances in our understanding of the functions of TGF-β superfamily members and their corresponding receptors, signaling pathways, and downstream molecular targets in regulating human extravillous trophoblasts invasion from studies using various in vitro or ex vivo experimental models.
[Trends in Endocrinology and Metabolism]
Mouse lineage tracing, organoid culture and single-molecule RNA in situ hybridizations revealed that the two epithelia derive from separate cervix-resident lineage-specific stem cell populations regulated by opposing Wnt signals from the stroma.
[Nature Cell Biology]
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Chumduri, C., Gurumurthy, R. K., Berger, H., Dietrich, O., Kumar, N., Koster, S., Brinkmann, V., Hoffmann, K., Drabkina, M., Arampatzi, P., Son, D., Klemm, U., Mollenkopf, H.-J., Herbst, H., Mangler, M., Vogel, J., Saliba, A.-E., & Meyer, T. F. (2021). Opposing Wnt signals regulate cervical squamocolumnar homeostasis and emergence of metaplasia. Nature Cell Biology, 1–14. https://doi.org/10.1038/s41556-020-00619-0 Cite
Investigators demonstrated the use of human small intestinal organoids to model ischemia-reperfusion injury by exposing organoids to hypoxia and reoxygenation.
[Cell Death & Disease]
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Kip, A. M., Soons, Z., Mohren, R., Duivenvoorden, A. A. M., Röth, A. A. J., Cillero-Pastor, B., Neumann, U. P., Dejong, C. H. C., Heeren, R. M. A., Olde Damink, S. W. M., & Lenaerts, K. (2021). Proteomics analysis of human intestinal organoids during hypoxia and reoxygenation as a model to study ischemia-reperfusion injury. Cell Death & Disease, 12(1), 1–13. https://doi.org/10.1038/s41419-020-03379-9 Cite
CRISPR/Cas9-mediated ARID1A knockout in primary TP53-/- human gastric organoids induced morphologic dysplasia, tumorigenicity and mucinous differentiation.
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Lo, Y.-H., Kolahi, K. S., Du, Y., Chang, C.-Y., Krokhotin, A., Nair, A., Sobba, W. D., Karlsson, K., Jones, S. J., Longacre, T. A., Mah, A. T., Tercan, B., Sockell, A., Xu, H., Seoane, J. A., Chen, J., Shmulevich, I., Weissman, J. S., Curtis, C., … Kuo, C. J. (2021). A CRISPR/Cas9-engineered ARID1A-deficient human gastric cancer organoid model reveals essential and non-essential modes of oncogenic transformation. Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-20-1109 Cite