Cell Models and Omics Techniques for the Study of Nonalcoholic Fatty Liver Disease: Focusing on Stem Cell-Derived Cell Models

Abstract

Nonalcoholic fatty liver disease (NAFLD) is now the leading cause of chronic liver disease in western countries. The molecular mechanisms leading to NAFLD are only partially understood, and effective therapeutic interventions are clearly needed. Therefore, preclinical research is required to improve knowledge about NAFLD physiopathology and to identify new therapeutic targets. Primary human hepatocytes, human hepatic cell lines, and human stem cell-derived hepatocyte-like cells exhibit different hepatic phenotypes and have been widely used for studying NAFLD pathogenesis. In this paper, apart from employing the different in vitro cell models for the in vitro assessment of NAFLD, we also reviewed other approaches (metabolomics, transcriptomics, and high-content screening). We aimed to summarize the characteristics of different cell types and methods and to discuss their major advantages and disadvantages for NAFLD modeling.

Establishment of Co-Culture Model of Primary Mature Adipocytes and Hepatocytes in Non-Alcoholic Fatty Liver Model Rats and its Effect on Hepatocyte Steatosis

“…Therefore, the establishment of NAFL adipocyte and hepatocyte co-culture model is of great significance for NAFL adipocyte and hepatocyte communication mechanism and drug testing studies [9] . At present, in the construction of co-culture system of adipocytes and hepatocytes, immortal cell lines are mostly used to study the effect of normal adipocytes on hepatocytes [10][11][12] . However, immortal cell lines lose their function in vivo due to their unlimited proliferation and immortalization characteristics, while primary cells retain their function in organs in vivo to a greater extent and are the cell models that best mimic the physiological and pathological conditions in vivo [7] .…”

Plastic compounds and liver diseases: Whether bisphenol A is the only culprit

“…94 ics and high-content screening). 96 Nguyen et al evaluated the sex-and age-related effects of prenatal BPA exposure on altered transcriptome and proteome profiles of hepatic lipid homeostasis in rat offspring using the multiomics approach. 97 These studies indicate oxidative stress as an important participant of BPA-induced liver disease which if not managed in time can lead to liver fibrosis development, leading to cirrhosis and hepatocellular carcinoma (HCC).…”

“…Pelecha et al. have summarized the characteristics of different cell types and methods for the in vitro assessment of NAFLD by reviewing other approaches (metabolomics, transcriptomics and high‐content screening) 96 . Nguyen et al.…”

Insect Cell-Based Models: Cell Line Establishment and Application in Insecticide Screening and Toxicology Research

“…Omics can further supplement phenotype-based screenings by catching system-wide molecular responses including mRNA transcripts, proteins, metabolites and other biomolecules. In return, this could help in detecting toxic potencies, elucidating mechanisms and identifying biomarkers [ 123 , 124 , 125 ].…”