ReviewArchives of toxicology2013
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.
Review in Archives of toxicology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 544 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
544 citing papers in PubMed.
- A targeted lipidomics workflow for high-throughput phenotyping and mechanism-based in vitro hepatotoxicity studies.Toxicology in vitro : an international journal published in association with BIBRA · 2026Article
- Developmental Environmental Chronotoxicity by Polystyrene Nanoplastics Exacerbates High-Fat Diet-Induced Pediatric MAFLD Through Circadian Disruption and Mitochondrial Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Free Fatty acid-induced disruption of hepatic vitamin D metabolism impairs bone homeostasis in an in vitro 3D human liver-bone model.Archives of toxicology · 2026Article
- The use of cultured human hepatocytes as a test system to evaluate cell proliferation as a key event in nongenotoxic carcinogenesis.Archives of toxicology · 2026Article
- Harnessing intermediate-scale bioreactors for next-generation macrophage production and application.Nature protocols · 2026Review
- Hepatokines lipocalin 2 and osteopontin drive muscle atrophy in MASH.Molecular metabolism · 2026Article
- Three-dimensional organoid culture enhances functional maturation of human pluripotent stem cell-derived hepatocytes.Molecular biology reports · 2026Article
- Physiologically relevant media are associated with overlapping metabolic responses in primary human hepatocytes and Huh7 cells.Physiological reports · 2026Article
- A genomic-led strategy to anticipate drug safety effects.PLoS genetics · 2026Article
- Exogenous adiponectin attenuates lipid accumulation and is associated with enhanced TG and VLDL secretion in primary chicken hepatocytes.Poultry science · 2026Article
- Inhibition of ceramide synthesis ameliorates body wasting in a cancer cachexia model.The Journal of clinical investigation · 2026Article
- Physiologically relevant 3D CRISPR screening enhances mechanistic insight into chemical toxicity compared to 2D screening.Toxicology · 2026Article
- The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of molecular sciences · 2026Review
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- Single-cell transcriptomics of acetaminophen-induced responses in human 2D and 3D liver microtissues.Archives of toxicology · 2026Article
- Advances and applications of organ-on-a-chip technology.Cell reports methods · 2026Review
- Nanostructured Lipid Carriers as Physicochemical Modulators of Complex Natural Extracts: Release Behavior and Bile-Induced Remodeling in Biorelevant Media.Molecules (Basel, Switzerland) · 2026Article
- Semi-automated isolation of parenchymal and non-parenchymal liver cells from mice and humans with enhanced stellate cell fraction.Cell & bioscience · 2026Article
- Three-Dimensional Culture of Primary Hepatocytes in a Single-Cell Layer on Poly(vinyl alcohol) Nanofibrous Membrane.International journal of molecular sciences · 2026Article
- Liver-on-a-Chip (LoC) Models: Case Studies of Academic Platforms and Commercial Products.Molecular pharmaceutics · 2026Review
484 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
93 authors.
Funding
Abstract
This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4α, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4α), resulting in up- and downregulation of hundreds of genes. An understanding of these changes is crucial for a correct interpretation of in vitro data. The possibilities and limitations of the most useful liver in vitro systems are summarized, including three-dimensional culture techniques, co-cultures with non-parenchymal cells, hepatospheres, precision cut liver slices and the isolated perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell-derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is given of the state of the art of liver in vitro and mathematical modeling systems that are currently used in the pharmaceutical industry with an emphasis on drug metabolism, prediction of clearance, drug interaction, transporter studies and hepatotoxicity. One key message is that despite our enthusiasm for in vitro systems, we must never lose sight of the in vivo situation. Although hepatocytes have been isolated for decades, the hunt for relevant alternative systems has only just begun.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.