Enhanced oxygen availability improves liver-specific functions of the AMC bioartificial liver.
Long-term culturing of primary porcine hepatocytes (PPH) inside the Academic Medical Center (AMC)-bioartificial liver is characterized by increased anaerobic glycolysis. Recommendations to increase oxygen availability were proposed in a previous numerical study and were experimentally evaluated in this study. Original bioreactors as well as new configuration bioreactors with 2.2-fold thinner nonwoven matrix and 2-fold more capillaries were loaded with PPHs and oxygenated with different gas oxygen pressures resulting in medium pO(2) (pO(2-med)) of either 135-150 mm Hg or 235-250 mm Hg. After 6 days culturing, new configuration bioreactors with pO(2-med )of 250 mm Hg showed significantly reduced anaerobic glycolysis, 60% higher liver-specific functions, and increased transcript levels of five liver-specific genes compared to the standard bioreactor cultures. Changed bioreactor configuration and increasing pO(2-med) contributed equally to these improvements. Histological examination demonstrated small differences in cell organization. In conclusion, higher metabolic stability and liver-specific functionality was achieved by enhanced oxygen availability based on a prior modeling concept.
Poyck
Paul P C
PP
Department of Surgery (Surgical Laboratory), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Mareels
Guy
G
Hoekstra
Ruurdtje
R
van Wijk
Albert C W A
AC
van der Hoeven
Tessa V
TV
van Gulik
Thomas M
TM
Verdonck
Pascal R
PR
Chamuleau
Robert A F M
RA
D000818:Animals; D019149:Bioreactors; D018914:Cells, Immobilized / Q000378:metabolism; D005260:Female; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000502:physiology*; D008111:Liver Function Tests; D019164:Liver, Artificial; D010100:Oxygen / Q000378:metabolism*; D010107:Oxygenators, Membrane; D034421:Sus scrofa / Q000502:physiology
D010100:Oxygen