Article ; Online: Development of a human liver microphysiological co-culture system for higher throughput chemical safety assessment.
Toxicological sciences : an official journal of the Society of Toxicology
2024
Abstract: Chemicals in the systemic circulation can undergo hepatic xenobiotic metabolism, generate metabolites and exhibit altered toxicity compared to their parent compounds. This paper describes a two-chamber liver-organ co-culture model in a higher-throughput ... ...
| Abstract | Chemicals in the systemic circulation can undergo hepatic xenobiotic metabolism, generate metabolites and exhibit altered toxicity compared to their parent compounds. This paper describes a two-chamber liver-organ co-culture model in a higher-throughput 96-well format for the determination of toxicity on target tissues in the presence of physiologically relevant human liver metabolism. This two-chamber system is a hydrogel formed within each well consisting of a central well (target tissue) and an outer ring-shaped trough (human liver tissue). The target tissue chamber can be configured to accommodate a three-dimensional (3D) spheroid-shaped microtissue, or a two-dimensional (2D) cell mono-layer. Culture medium and compounds freely diffuse between the two chambers. Human differentiated HepaRGTM liver cells are used to form the 3D human liver microtissues, which displayed robust protein expression of liver biomarkers (albumin, asialoglycoprotein receptor, Phase I cytochrome P450 (CYP3A4) enzyme, multidrug resistance-associated protein 2 transporter, and glycogen), and exhibited Phase I/II enzyme activities over the course of 17 days. Histological and ultrastructural analyses confirmed that the HepaRG microtissues presented a differentiated hepatocyte phenotype, including abundant mitochondria, endoplasmic reticulum and bile canaliculi. Liver microtissue zonation characteristics could be easily modulated by maturation in different media supplements. Furthermore, our proof-of-concept study demonstrated the efficacy of this co-culture model in evaluating testosterone-mediated androgen receptor responses in the presence of human liver metabolism. This liver-organ co-culture system provides a practical, higher-throughput testing platform for metabolism-dependent bioactivity assessment of drugs/chemicals, to better recapitulate the biological effects and potential toxicity of human exposures. |
|---|---|
| Language | English |
| Publishing date | 2024-02-09 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 1420885-4 |
| ISSN | 1096-0929 ; 1096-6080 |
| ISSN (online) | 1096-0929 |
| ISSN | 1096-6080 |
| DOI | 10.1093/toxsci/kfae018 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 1709: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.