Hepatocyte function in a hollow fiber bioreactor: a potential bioartificial liver.
We have developed a novel hepatocyte loaded hollow fiber bioreactor as a potential bioartificial liver. Freshly harvested rat hepatocytes were entrapped in a three-dimensional gel matrix within hollow fibers in a perfused bioreactor. Gel entrapment allowed cells to be cultured at high density while maintaining tissue-specific function. Hepatocyte function was evaluated in 10 bioreactors, each containing approximately 5 x 10(7) cells. Oxygen consumption averaged 0.32 pmole/cell/hr, albumin appearance averaged 0.60 pg/cell/hr, and lidocaine clearance (a measure of the P-450 activity) averaged 0.74 pg/cell/hr. Function persisted for the 7 days of the study. Electron microscopy at 7 days showed the distinctive ultrastructure of viable, differentiated hepatocytes: bile canaliculi, intercellular junctions, peroxisomes, abundant mitochondria, and glycogen granules. Maintenance of tissue specific function and ultrastructure suggests that this bioreactor configuration has potential as a device to support patients in liver failure, as well as to study hepatocytes in vitro.
Shatford
R A
RA
Department of Surgery, University of Minnesota, Minneapolis 55455.
Nyberg
S L
SL
Meier
S J
SJ
White
J G
JG
Payne
W D
WD
Hu
W S
WS
Cerra
F B
FB
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001187:Artificial Organs; D002454:Cell Differentiation; D002470:Cell Survival; D005782:Gels; D008012:Lidocaine / Q000493:pharmacokinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D010101:Oxygen Consumption; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism; D013997:Time Factors
D000596:Amino Acids; D005782:Gels; D012709:Serum Albumin; D008012:Lidocaine