Drug-induced liver injury is the most important safety-related reason of drug withdrawal during the pre- and post-marketing stages of drug development. Hepatic in vitro systems capable of screening out toxic compounds early in the process are therefore of key importance. Traditionally, cultures of primary animal and human hepatocytes are used, but their robustness is compromised by limited lifespan and quick loss of metabolic functions.
Our group offers an alternative to primary rodent hepatocytes:
Hepatic cell line derived from hepatic progenitors of biliary origin
Liver epithelial cells (rLEC) of biliary origin were originally derived from 10 days-old rats and express markers typical for hepatic progenitors. Indeed, when exposed to hepatogenic growth factors, hepatocyte-like cells are obtained that demonstrate phenotypical features of functional hepatocytes, namely;
- expression and nuclear localization of liver-specific transcription factors,
- expression and polarization of drug transporters,
- expression of plasma proteins and typical building blocks of hepatic intercellular communication,
- activity of drug metabolizing enzymes at a level similar to primary hepatocytes.
Also improved expression of carbohydrate, lipid, vitamin and mineral metabolism markers was evidenced.
- non-tumour derived,
- easily cryopreservable and expandable in the in vitro setting; from 1 Mio of cryopreserved rLECs to 300 Mio of cells in less than 2 weeks time,
- stable expression of hepatic progenitor markers for at least 15 consecutive passages,
- cost of 300 Mio undifferentiated rLECs comparable to the purchase cost of 5 Mio of primary rodent cells, or the cost of one in-house rodent hepatocyte isolation, yet no animal handling required,
- elimination of the interindividual variability associated with the use of animals,
- rLEC-derived hepatocyte-like cells maintain normal levels of drug metabolizing enzymes for several weeks,
- cell bank of more than 150 Mio cryopreserved rLECs available, including enhanced green fluorescent protein (GFP)- and firefly luciferase-transduced cells.
Granted EP patent “Differentiation of rat liver epithelial cells into hepatocyte-like cells“, EP2041272 (B1), US patent pending US2010/278782 (A1)
Undifferentiated rLEC and rLEC-derived hepatocytes could be applicable in safety screens of new chemical entities as routinely performed in:
- the cosmetic industry, where animal testing and marketing bans became final in March 2013, irrespective of the availability of alternative non-animal tests,
- the pharmaceutical industry, where in vitro methods become key for early decision making in the drug development process due to their speed, high throughput and cost-effectiveness,
- the chemical industry, where safety testing under REACH is associated with substantial financial costs and high animal consumption.
What are we looking for?
- Out-licensing of the rLECs hepatogenic differentiation technology (EP2041272 (B1)),
- Selling of the rLECs cell bank,
- Setting up joint R&D projects with industrial partners to develop toxicological assays based on rLECs,
- Providing expertise in the area of (hepatic) stem cell differentiation technologies on fee-for-service or collaborative basis.
Customer-tailored solutions are also discussable.
Interested parties can contact:
Mrs. Manon Vivier
+32 (0)2 477 45 19