Development of a small-scale bioreactor for drug metabolism studies maintaining hepatospecific functions.
1. The aim of the study was the development of a small-scale liver cell bioreactor maintaining tissue monoxygenase activity and hepatospecific activities over at least 2 weeks. 2. For characterization the antihypertensive drug urapidil was used as a model compound to study maintenance of metabolic activity. Tissue-specific parameters assessed included urea and albumin secretion as well as cellular integrity. The problem of the use of serum in bioreactor cultures is addressed. 3. Bioreactor runs could be performed in serum- and lactate-free cultures with a joint recovery of oxidative biotransformation capacity for urapidil as well as tissue-specific markers. LDH release was reduced with older cultures. Fibronectin was shown as a contributing factor for cell attachment. 4. In the present study the design and function of a modular, small-scale-type bioartificial liver cell culture model is thus described lending itself for drug metabolism studies but maintaining also typical hepatospecific properties.
Leibniz Laboratories of Biotechnology and Artificial Organs, Medizinische Hochschule, Hannover, Germany.
A
A
Bader
N
N
Frühauf
K
K
Zech
A
A
Haverich
J T
JT
Borlak
D000418:Albumins / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents; D019149:Bioreactors; D002448:Cell Adhesion; D002470:Cell Survival; D016895:Culture Media, Serum-Free; D005260:Female; D005312:Fetal Blood; D005353:Fibronectins / Q000502:physiology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010879:Piperazines / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D014508:Urea / Q000378:metabolism
D000418:Albumins; D000959:Antihypertensive Agents; D016895:Culture Media, Serum-Free; D005353:Fibronectins; D004364:Pharmaceutical Preparations; D010879:Piperazines; D014508:Urea; C015568:urapidil; D007770:L-Lactate Dehydrogenase