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| Content Provider | Springer Nature Link |
|---|---|
| Author | Bazou, Despina |
| Copyright Year | 2009 |
| Abstract | This paper describes the alginate encapsulation of preformed high-density 3-D HepG2 cell aggregates that guarantees good maintenance of liver-specific biomarker expression. The process involves forming a high-density (≥7 × 104 cells/aggregate) discoid 3-D cell aggregate in an ultrasound trap, which is subsequently recovered and encapsulated in alginate/CaCl2 hydrogel. Glucose secretion/consumption, lactate release, detoxifying enzyme capacity, cytokeratin-18 expression as well as hypoxia were characterized in encapsulated 3-D HepG2 aggregates over 10 days in culture. Encapsulated 3-D HepG2 aggregates released glucose into the media, although this ability was exhibited only after 1 day in culture and was subsequently lost over the ensuing 9 days. In contrast, lactate was constantly released into the media. Significantly more lactate was secreted after 3 days in culture indicating a more hypoxic environment and hence a higher rate of anaerobic glycolysis. Aggregates consistently expressed cytokeratin-18. Cytochrome P450-1A1 activity reached a maximum on day 1 of culture followed by a progressive reduction to basal levels, while P450-3A4 activity was up-regulated in a time-dependent manner reaching a peak on day 7 in culture. Glutathione-S-transferase activity, on the other hand, was at more physiological levels and remained constant over the 10-day culture period. The ultrasound trap allowed the rapid (within 5 min) generation of uniformly shaped and sized aggregates. The results reported here suggest that ultrasound-formed 3-D HepG2 aggregates can serve as alternative in vitro models providing a quick outlook on toxicity, in a tissue-mimetic manner, thus offering the future option of a cost-effective screening platform for pharmaceutical development. |
| Starting Page | 127 |
| Ending Page | 141 |
| Page Count | 15 |
| File Format | |
| ISSN | 07422091 |
| Journal | Cell Biology and Toxicology |
| Volume Number | 26 |
| Issue Number | 2 |
| e-ISSN | 15736822 |
| Language | English |
| Publisher | Springer Netherlands |
| Publisher Date | 2009-03-21 |
| Publisher Place | Dordrecht |
| Access Restriction | Subscribed |
| Subject Keyword | Drug metabolism Cytokeratin-18 Encapsulation Glucose Hypoxia Ultrasound trap Biochemistry Pharmacology/Toxicology Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Health, Toxicology and Mutagenesis Toxicology |
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