Alginate-encapsulated HepG2 cells in a fluidized bed bioreactor maintain function in human liver failure plasma.
Alginate-encapsulated HepG2 cells cultured in microgravity have the potential to serve as the cellular component of a bioartificial liver. This study investigates their performance in normal and liver failure (LF) human plasma over 6-8 h in a fluidized bed bioreactor. After 8 days of microgravity culture, beads containing 1.5 x 10(9) cells were perfused for up to 8 h at 48 mL/min with 300 mL of plasma. After exposure to 90% LF plasma, vital dye staining showed maintained cell viability, while a 7% increase in lactate dehydrogenase activity indicated minimal cell damage. Glucose consumption, lactate production, and a 4.3-fold linear increase in alpha-fetoprotein levels were observed. Detoxificatory function was demonstrated by quantification of bilirubin conjugation, urea synthesis, and Cyp450 1A activity. These data show that in LF plasma, alginate-encapsulated HepG2 cells can maintain viability, and metabolic, synthetic, and detoxificatory activities, indicating that the system can be scaled-up to form the biological component of a bioartificial liver.
Coward
Sam M
SM
Centre for Hepatology, Royal Free Hospital and UCL Medical School, London, UK.
Legallais
Cécile
C
David
Bertrand
B
Thomas
Michael
M
Foo
Ying
Y
Mavri-Damelin
Demetra
D
Hodgson
Humphrey J
HJ
Selden
Clare
C
D000418:Albumins / Q000378:metabolism; D000464:Alginates / Q000737:chemistry*; D000641:Ammonia / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism; D019149:Bioreactors; D002470:Cell Survival; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D018914:Cells, Immobilized / Q000166:cytology / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry; D056945:Hep G2 Cells / Q000166:cytology / Q000378:metabolism*; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017093:Liver Failure / Q000628:therapy*; D019164:Liver, Artificial; D010949:Plasma / Q000378:metabolism*; D000637:Transaminases / Q000378:metabolism
D000418:Albumins; D000464:Alginates; D006603:Hexuronic Acids; D000641:Ammonia; D020723:Glucuronic Acid; D007770:L-Lactate Dehydrogenase; D000637:Transaminases; D005947:Glucose; D001663:Bilirubin