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We developed multicellular liver microtissues composed of hepatic stellate cells, hepatoblastoma cells and human umbilical vein endothelial cells. The microtissues were supplemented with a combination of palmitic acid and oleic acid to develop fibrosis models. Subsequently, various groups of microtissues were exposed to SIM and SIM\u2010LipoNPs at doses of 5 and 10\u2009mg\/mL. The effectiveness of the treatments was evaluated by analysing cell viability, production of reactive oxygen species (ROS) and nitric oxide (NO), the expression of Kruppel\u2010like factor (KLF) 2, and pro\u2010inflammatory cytokines (interleukin(IL)\u20101 \u03b1, IL\u20101 \u03b2, IL\u20106 and tumour necrosis factor\u2010\u03b1), and the expression of collagen I. Our results indicated that SIM\u2010LipoNPs application showed promising results. SIM\u2010LipoNPs effectively amplified the SIM\u2010klf2\u2010NO pathway at a lower dosage compatible with a high dosage of free SIM, which also led to reduced oxidative stress by decreasing ROS levels. SIM\u2010LipoNPs administration also resulted in a significant reduction in pro\u2010inflammatory cytokines and Collagen I mRNA levels, as a marker of fibrosis. In conclusion, our study highlights the considerable therapeutic potential of using SIM\u2010LipoNPs to prevent liver fibrosis progress, underscoring the remarkable properties of SIM\u2010LipoNPs in activating the KLF2\u2010NO pathway and anti\u2010oxidative and anti\u2010inflammatory response.<\/jats:p>","DOI":"10.1111\/jcmm.18529","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T13:46:32Z","timestamp":1720619192000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The effects of simvastatin\u2010loaded nanoliposomes on human multilineage liver fibrosis microtissue"],"prefix":"10.1111","volume":"28","author":[{"given":"Shima","family":"Parsa","sequence":"first","affiliation":[{"name":"Shiraz Institute for Stem Cell &amp; Regenerative Medicine Shiraz University of Medical Sciences  Shiraz 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