HEPATOCYTE FUNCTION IN A HOLLOW FIBER BIOREACTOR - A POTENTIAL BIOARTIFICIAL LIVER

被引:79
作者
SHATFORD, RA
NYBERG, SL
MEIER, SJ
WHITE, JG
PAYNE, WD
HU, WS
CERRA, FB
机构
[1] UNIV MINNESOTA,DEPT CHEM ENGN & MAT SCI,MINNEAPOLIS,MN 55455
[2] UNIV MINNESOTA,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455
基金
美国国家科学基金会;
关键词
D O I
10.1016/0022-4804(92)90253-V
中图分类号
R61 [外科手术学];
学科分类号
摘要
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 × 107 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. © 1992.
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页码:549 / 557
页数:9
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