[Liver cell culture in bioreactors for in vitro drug studies as an alternative to animal testing].
An important consideration for the utilisation of in vitro culture models for studies on drug metabolism as an alternative to animal testing is the maintenance of a defined degree of cell differentiation. Thus, in vitro conditions reflecting as near as possible the in vivo situation of the cells within the whole organ are required. A bioreactor was developed for the cultivation of liver cells which allows the reorganisation of hepatocytes and non-parenchymal cells of the liver in coculture to form three-dimensional, tissue-like structures including extracellular matrix components produced by the cells. In this study, the vitality and metabolic activity of isolated rat hepatocytes was investigated over a two week culture period in bioreactors. The results show that after a reorganisation phase, the cells preserve specific functions, such as protein and urea synthesis capacity and specific cytochrome P450 activities during the culture period, with maximal values during the first week. Possible applications of the model in pharmaceutical industry are studies on metabolite patterns, enzyme induction, drug-drug-interactions, first pass effects and long-term toxicity of drugs.
Zeilinger
K
K
Experimentelle Chirurgie, Humboldt-Universität, D-Berlin.
Auth
S
S
Unger
J
J
Grebe
A
A
Mao
L
L
Petrik
M
M
Holland
G
G
Appel
K
K
Nüssler
A
A
Neuhaus
P
P
Gerlach
J
J
D000826:Animal Testing Alternatives; D000818:Animals; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003374:Coumarins / Q000493:pharmacokinetics; D022781:Hepatocytes / Q000166:cytology; D008099:Liver / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D010078:Oxazines / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
D003374:Coumarins; D010078:Oxazines; C017299:7-ethoxycoumarin; C007649:ethoxyresorufin