Multi-cellular hepatocellular carcinoma (HCC) organoid models were established which contained various types of stromal cells, such as hepatic stellate cells, fibroblasts, and endothelial cells together with HCC cells.
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The authors describe the mechanisms of tissue repair following damage, highlighting the close relationship between inflammation and liver regeneration, and discuss how recent findings can help design novel therapeutic approaches.
[Nature Reviews Molecular Cell Biology]
The proteomics studies on liver co-cultures implicated the activated hepatic stellate cells-secreted chemokine CXCL12 in the induction of NK cell quiescence through its cognate receptor CXCR4.
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Correia, A. L., Guimaraes, J. C., Auf der Maur, P., De Silva, D., Trefny, M. P., Okamoto, R., Bruno, S., Schmidt, A., Mertz, K., Volkmann, K., Terracciano, L., Zippelius, A., Vetter, M., Kurzeder, C., Weber, W. P., & Bentires-Alj, M. (2021). Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy. Nature, 1–6. https://doi.org/10.1038/s41586-021-03614-z Cite
Scientists established liver fibrosis models using multicellular tumor spheroids (MCTSs) composed of hepatocellular carcinoma (HCC) and stromal cells such as fibroblasts (WI38), hepatic stellate cells (LX2), and endothelial cells (HUVEC) seeded at constant ratios.
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The authors established mouse models of CCl4-injured liver fibrosis (LF) and administered hPMSCs at different stages of LF once a week for two weeks. The therapeutic effect of hPMSCs on LF was investigated, according to histopathological and blood biochemical analyses.
[Stem Cell Research & Therapy]
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Investigators evaluated the hypothesis that myofibroblastic (activated) hepatic stellate cells and liver fibrosis could be safely reduced by inhibiting the cysteine/glutamate antiporter xCT.
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Du, K., Oh, S. H., Dutta, R. K., Sun, T., Yang, W.-H., Chi, J.-T. A., & Diehl, A. M. (n.d.). Inhibiting xCT/SLC7A11 induces ferroptosis of myofibroblastic hepatic stellate cells but exacerbates chronic liver injury. Liver International, n/a(n/a). https://doi.org/https://doi.org/10.1111/liv.14945 Cite
Researchers investigated the Fas/FasL signaling and hepatocytes apoptosis in liver samples from both human sections and mouse models.
[Cell Death & Disease]
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Investigators provide an in-depth discussion of the underlying pathogenetic mechanisms that lead to progressive liver injury, including the metabolic origins of Nonalcoholic fatty liver disease (NAFLD), the effect of NAFLD on hepatic glucose and lipid metabolism, bile acid toxicity, macrophage dysfunction, and hepatic stellate cell activation, and consider the role of genetic, epigenetic, and environmental factors that promote fibrosis progression and risk of hepatocellular carcinoma in nonalcoholic steatohepatitis.
The authors postulated the hypothesis that DDR1 and its ligand might ignite the interaction between uveal melanoma (UM) cells and their surrounding niche of liver thereby conferring strengthened survival, proliferation, stemness and eventually promoting metastatic colonization in liver.
[Signal Transduction and Targeted Therapy]
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Investigators found that glucocorticoid-induced leucine zipper deficiency in mice was associated with elevated CCL2 production and pro-inflammatory leukocyte infiltration at the early liver fibrosis (LF) stage, resulting in enhanced LF development.
[Cell Death & Disease]
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Flamini, S., Sergeev, P., Viana de Barros, Z., Mello, T., Biagioli, M., Paglialunga, M., Fiorucci, C., Prikazchikova, T., Pagano, S., Gagliardi, A., Riccardi, C., Zatsepin, T., Migliorati, G., Bereshchenko, O., & Bruscoli, S. (2021). Glucocorticoid-induced leucine zipper regulates liver fibrosis by suppressing CCL2-mediated leukocyte recruitment. Cell Death & Disease, 12(5), 1–13. https://doi.org/10.1038/s41419-021-03704-w Cite
Scientists demonstrated that serum amyloid A1 (SAA1) acts as a chemokine recruiting HSCs towards injury loci signaling via TLR2, a finding proven by gene manipulation studies in cell and mice models.
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Getachew, A., Abbas, N., You, K., Yang, Z., Hussain, M., Huang, X., Cheng, Z., Tan, S., Tao, J., Yu, X., Chen, Y., Yang, F., Pan, T., Xu, Y., Xu, G., Zhuang, Y., Wu, F., & Li, Y. (2021). SAA1/TLR2 axis directs chemotactic migration of hepatic stellate cells responding to injury. IScience, 0(0). https://doi.org/10.1016/j.isci.2021.102483 Cite