Microgravity spheroids as a reliable, long term tool for predicitive toxicology

S. J. Fey (Foredragsholder)

Aktivitet: Foredrag og mundtlige bidragForedrag og præsentationer i privat eller offentlig virksomhed

Beskrivelse

Spheroids grown in rotating ‘microgravity’ bioreactors (MC2 Biotek) from human C3A cells (an immortal hepatocellular carcinoma cell line) have been shown to need 18 days to reach maturity (as determined by their growth rate, viability and their production of urea, cholesterol and ATP). After this time they are metabolically stable for at least 24 days more; grow slowly (a doubling time of >20 days); produce physiological levels of urea, cholesterol and ATP; exhibit stable gene expression (for selected liver relevant genes); and can post translationally modify proteins in a manner which mirrors those seen in vivo. Studies with 5 common drugs (acetaminophen, amiodarone, metformin, phenformin, and valproic acid) have shown that they are more predictive of lethally-toxic plasma levels in vivo than published studies using primary human hepatocytes. Shotgun proteomics has revealed that the gain of in vivo-like physiological properties is due to an exquisitely subtle modulation of the levels of hundreds of cellular proteins.
Wrzesinski et al. Toxicology Research http://xlink.rsc.org/?doi=C3TX20086H
Periode2. sep. 2013
BegivenhedstitelEurotox 2013: 49th Congress of the European Societies of Toxicology (EUROTOX)
BegivenhedstypeKonference
Konferencenummer49
PlaceringInterlaken, Schweiz