期刊
ARTIFICIAL ORGANS
卷 25, 期 9, 页码 740-748出版社
WILEY
DOI: 10.1046/j.1525-1594.2001.06669.x
关键词
ammonia detoxification; isolated porcine hepatocytes; lidocaine metabolism; liver support systems; radial-flow bioreactor; urea synthesis
To overcome the limitations of standard hollow-fiber module in ensuring efficient cell perfusion and long-term expression of highly differentiated hepatocyte functions, we developed a novel bioreactor in which a three-dimensional hepatocyte culture system was perfused in radial-flow geometry. Isolated porcine hepatocytes were cultured for 2 weeks in recirculating serum-free tissue culture medium, in which NH4Cl and lidocaine were repeatedly added, and ammonia removal, urea synthesis, monoethylglycinexylide (MEGX) production, albumin secretion, PO2, PCO2, O-2 consumption, and pH were measured thereafter. During the whole duration of the study, ammonia removal was paralleled by urea production, while MEGX concentration was constantly increased. Our results indicated that hepatocytes remained differentiated and metabolically active throughout the duration of the study. The radial-flow bioreactor allowed physiological contact between recirculating fluid and cells by equalizing the concentration of the perfusing components, including O-2 throughout the module, suggesting a potential use of this configuration for extracorporeal liver support.
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