Characterisation of some cytotoxic endpoints using rat liver and HepG2 spheroids as in vitro models and their application in hepatotoxicity studies. II. Spheroid cell spreading inhibition as a new cytotoxic marker

Stable immobilization of rat hepatocyte spheroids on galactosylated nanofiber scaffold

“…Numerous microvilli also dotted around spheroid surface. These spheroids closely resembled the functional spheroids reported in literature, which exhibited tight cell-cell contact [5], in contrast with those rough and bumpy spheroids that are damaged by toxicants [34].…”

Engineering liver tissue spheroids with inverted colloidal crystal scaffolds

“…Under these conditions, the necessity ability for real-time visualization of spheroids at different depths and specific locations [21] was possible. The cell viability at the center of spheroids was also directly confirmed by transferring individual spheroids to a 2D tissue culture plate where they disassembled and fully spread in a few days [31] (Fig. 6).…”

Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME

“…15 Human hepatocytesPure primary hepatocytes3–4 weeks culture in bioreactor possible, maintained hepatocyte functionality (Albumin, CYP3A4, HNF4a, bile canaliculi)Tostoes et al (2011)Pure HepG2Bile canalicular network with MRP-2 expression, increased albumin synthesis. Differential gene expression in comparison with 2D cultureKelm et al (2003; 2004); Mueller et al (2011); Xu et al (2003); Oshikata et al (2011)HepG2 co-culture with endothelial cellsHUVECs surround the HepG2 core.Kelm et al (2004)Primary mouse hepatocytesPrimary hepatocytesHigher expression of CYP1A2 in monolayer.Nemoto and Sakurai (1992)Primary hepatocytes in co-culture with NIH3t3Increased albumin secretion, Ammonia elimination rates, CYP1A2 activity.Seo et al (2006b)Primary hepatocytes in co-culture with NPCsUpregulation of albumin secretion and CYP1A2 activityKojima et al (2009)…”

“…Other evaluated end points, such as pyruvate uptake, galactose biotransformation and lactate release, were less sensitive than glucose secretion. Moreover, the compounds, such as propanol, galactosamine, diclofenac and acetaminophen, had a negative impact on anchorage dependence, cellular morphology and cell spreading (Xu et al 2003) of spheroids. Other reports suggested that rat hepatocyte spheroids were not useful for drug testing, since they were not sensitive to methotrexate treatment (Walker et al 2000), whereas 2D culture displayed sensitivity.…”