8511 HTS DILI
| Reference number | |
| Coordinator | Karolinska Institutet - Institutionen för fysiologi och farmakologi |
| Funding from Vinnova | SEK 1 501 117 |
| Project duration | November 2013 - October 2015 |
| Status | Completed |
Purpose and goal
The purpose was to improve the micro analysis system, liver in vitro for longer periods of time. Over 90% of the planned results and 76% of expected milestones were achieved. Project results were presented at least 10 scientific conferences and exhibitions as well as manuscripts are soon ready to be sent in for publication
Results and expected effects
The project aimed to gain a deeper understanding of the functions of the human liver using a spheroid model of liver cells in culture. We could show that the model, which consists of primary hepatocytes and Kupffer cells, shows excellent morphology and functionality for a long period, including a stable expression of the P450 enzymes and inducibility. Spheroids have de novo bile acid synthesis, bile acid uptake and stable expression of liver-specific components for a period of at least 28 days as also revealed by transcriptome and proteome analysis.
Approach and implementation
A new analysis was developed that identifies compounds responsible cholestatic toxicity with good predictability (sensitivity 67%, specificity 80%). Furthermore, we developed a scaled platform for microspheroids (Gravity TRAP / 384), which is in its last prototype phases and soon will go into production by InSphero.