An in vitro model using human colon organoids was established by 60 weeks of inflammatory stimulation. The key gene for mucosal injury caused by long-term inflammation was identified by microarray analysis. An in vivo model was established by xenotransplantation of organoids into mouse colonic mucosa.
[Journal of Crohns & Colitis]
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Watanabe, S., Nishimura, R., Shirasaki, T., Katsukura, N., Hibiya, S., Kirimura, S., Negi, M., Okamoto, R., Matsumoto, Y., Nakamura, T., Watanabe, M., & Tsuchiya, K. (2021). Schlafen 11 is a novel target for mucosal regeneration in Ulcerative Colitis. Journal of Crohn’s and Colitis, jjab032. https://doi.org/10.1093/ecco-jcc/jjab032 Cite
Crohn’s disease patient-derived intestinal organoids were characterized by differentiation gene markers and then exposed to TNF-α, IFN-γ, IL-1β or LPS, or IL-28A with or without GLPG0634.
[American Journal of Physiology-Gastrointestinal and Liver Physiology]
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Xu, P., Becker, H., Elizalde, M., Pierik, M., Masclee, A. A. M., & Jonkers, D. M. A. E. (2021). Interleukin-28A Induces Epithelial Barrier Dysfunction in CD Patient-derived Intestinal Organoids. American Journal of Physiology-Gastrointestinal and Liver Physiology. https://doi.org/10.1152/ajpgi.00064.2020 Cite
Scientists established iPSCs from two additional patients with different NPHS1 mutations and examined the podocyte abnormalities in kidney organoids derived from these cells.
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Ohmori, T., De, S., Tanigawa, S., Miike, K., Islam, M., Soga, M., Era, T., Shiona, S., Nakanishi, K., Nakazato, H., & Nishinakamura, R. (2021). Impaired NEPHRIN localization in kidney organoids derived from nephrotic patient iPS cells. Scientific Reports, 11(1), 3982. https://doi.org/10.1038/s41598-021-83501-9 Cite
Researchers performed genetic analyses of adenomatous polyposis coli using a 3D organoid culture of mouse colon epithelia, which enabled the detailed examination of epithelial properties.
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To study the roles of DNAJC6 in Parkinson’s disease (PD) pathogenesis, scientists used human ESCs with CRISPR-Cas9-mediated gene editing. They showed that DNAJC6 mutations cause key PD pathologic features, i.e., midbrain-type dopamine neuron degeneration, pathologic α-synuclein aggregation, increase of intrinsic neuronal firing frequency, and mitochondrial and lysosomal dysfunctions in human midbrain-like organoid.
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Wulansari, N., Darsono, W. H. W., Woo, H.-J., Chang, M.-Y., Kim, J., Bae, E.-J., Sun, W., Lee, J.-H., Cho, I.-J., Shin, H., Lee, S.-J., & Lee, S.-H. (2021). Neurodevelopmental defects and neurodegenerative phenotypes in human brain organoids carrying Parkinson’s disease-linked DNAJC6 mutations. Science Advances, 7(8), eabb1540. https://doi.org/10.1126/sciadv.abb1540 Cite
Human iPSCs has the potential to generate all cell types of a human body under 2D culture conditions or form organ like structures- organoids, under 3D culture conditions.
Scientists used multiple colorectal cancer (CRC) cell lines to investigate the growth-inhibitory effect of crenolanib and its effect in combination with other cytotoxic agents. Primary cultures of patient-derived organoids, a model that reflects the heterogeneity of clinical CRC, were used to further validate the effects of crenolanib.
[Molecular Cancer Research]
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Fujino, S., Miyoshi, N., Ito, A., Yasui, M., Ohue, M., Ogino, T., Takahashi, H., Uemura, M., Matsuda, C., Mizushima, T., Doki, Y., & Eguchi, H. (2021). Crenolanib regulates ERK and AKT/mTOR signaling pathways in RAS/BRAF-mutated colorectal cancer cells and organoids. Molecular Cancer Research. https://doi.org/10.1158/1541-7786.MCR-20-0600 Cite
Scientists discuss a novel strategy for neuropsychiatric drug discovery which aims to address limitations by identifying disease-related functional responses in a variety of patient-derived cells, such as induced pluripotent stem cell-derived neurons and organoids or peripheral blood mononuclear cells.
3D organoids were prepared from Grave’s orbitopathy (GO) related human orbital fibroblasts obtained from patients with GO.
[Experimental Eye Research]
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Ichioka, H., Ida, Y., Watanabe, M., Ohguro, H., & Hikage, F. (2021). Prostaglandin F2α and EP2 agonists, and a ROCK inhibitor modulate the formation of 3D organoids of Grave’s orbitopathy related human orbital fibroblasts. Experimental Eye Research, 108489. https://doi.org/10.1016/j.exer.2021.108489 Cite
Colibactin’s distinct mutational signature is reflected in human colorectal cancer, suggesting a causal link. Scientists investigated its transformation potential using organoids from primary murine colon epithelial cells.
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The authors demonstrated that optimized human intestinal organoids enable better simulation of the native human intestinal epithelium, and they were significantly more susceptible to EV-A71 than CVA16.
[Stem Cell Reports]
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