Article

Enhanced Oxygen Availability Improves Liver‐specific Functions of the AMC Bioartificial Liver

Academic Medical Center Liver Center, University of Amsterdam; and
Artificial Organs (impact factor: 2). 01/2008; 32(2):116 - 126. DOI:10.1111/j.1525-1594.2007.00500.x pp.116 - 126

ABSTRACT 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 pO2 (pO2-med) of either 135-150 mm Hg or 235-250 mm Hg. After 6 days culturing, new configuration bioreactors with pO2-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 pO2-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.

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    Article: An Emerging Paradigm in Tissue Engineering: From Chemical Engineering to Developmental Engineering for Bioartificial Tissue Formation through a Series of Unit Operations that Simulate the In Vivo Successive Developmental Stages†
    Petros Lenas
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Keywords

2.2-fold thinner nonwoven matrix
 
6 days culturing
 
60% higher liver-specific functions
 
anaerobic glycolysis
 
capillaries
 
cell organization
 
Changed bioreactor configuration
 
different gas oxygen pressures
 
higher metabolic stability
 
improvements
 
increase oxygen availability
 
Long-term culturing
 
new configuration bioreactors
 
oxygen availability
 
oxygenated
 
PPHs
 
primary porcine hepatocytes
 
prior modeling concept
 
Recommendations
 
standard bioreactor cultures