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. 2021 Sep 24;9:730008. doi: 10.3389/fbioe.2021.730008

TABLE 3.

Selected 3D NAFLD models established from different cell types.

Cell type Culture paradigm Exposure duration Endpoints/outcomes References
PHHs Spheroid mono-culture 48 h Hepatic lipid accumulation Bell et al. (2016)
PHHs Spheroid mono-culture 21 days Hepatic lipid accumulation Kozyra et al. (2018)
Transcriptional changes in genes associated with hepatic gluconeogenesis, glycolysis, and lipogenesis
PHHs Liver-on-a-chip mono-culture 14 days Hepatic lipid accumulation Kostrzewski et al. (2017)
Transcriptional changes in genes associated with insulin resistance and lipid metabolism
Increased inflammatory and fibrotic markers
PHHs MPCC co-culture 18 days Hepatic lipid accumulation Davidson et al. (2016)
Decreased sensitivity to insulin-mediated inhibition of glucose output and dysregulated insulin signaling
PHHs Liver-on-a-chipco-culture 10 days Hepatic lipid accumulation Feaver et al. (2016)
Decreased sensitivity to insulin-mediated inhibition of glucose output and dysregulated insulin signaling
Increased oxidative stress and apoptosis
Increased inflammatory analyte secretion and fibrogenic activation markers
HepG2 Gut–liver-on-a-chip co-culture 24 h Accumulated chylomicrons in HepG2 Lee & Sung (2018)
hiPSC-HLCs; hESC-HLCs Organoid tri-lineage 7 days Hepatic lipid accumulation Ouchi et al. (2019)
Increased inflammatory cytokines
Increased collagen production
Increased organoid stiffness

PHHs, primary human hepatocytes; MPCC, micropatterned co-culture; hESCs, human embryonic stem cells; hiPSCs, human induced pluripotent stem cells; HLCs, hepatocyte-like cells.