Hepatocyte function in a hollow fiber bioreactor: A potential bioartificial liver

Russell A. Shatford; Scott L. Nyberg; Steven J. Meier; James G. White; William D. Payne; Wei Shou Hu; Frank B. Cerra

doi:10.1016/0022-4804(92)90253-V

Hepatocyte function in a hollow fiber bioreactor: A potential bioartificial liver

Russell A. Shatford
, Scott L. Nyberg
, Steven J. Meier
, James G. White
, William D. Payne
, Wei Shou Hu
, Frank B. Cerra

Research output: Contribution to journal › Article › peer-review

83 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	549-557
Number of pages	9
Journal	Journal of Surgical Research
Volume	53
Issue number	6
DOIs	https://doi.org/10.1016/0022-4804(92)90253-V
State	Published - Dec 1992

Bibliographical note

Funding Information:
1 This research was supported in part by grants from the Whittaker Foundation and the National Science Foundation (BCS - 8915307). S.L.N. was supported by an Ethicon/Society of University Surgeons Research Fellowship. ’ Presented at the Annual Meeting of the Association for Academic Surgery, Colorado Springs, Colorado, November 20-23, 1991.

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title = "Hepatocyte function in a hollow fiber bioreactor: A potential bioartificial liver",

abstract = "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.",

author = "Shatford, \{Russell A.\} and Nyberg, \{Scott L.\} and Meier, \{Steven J.\} and White, \{James G.\} and Payne, \{William D.\} and Hu, \{Wei Shou\} and Cerra, \{Frank B.\}",

note = "Funding Information: 1 This research was supported in part by grants from the Whittaker Foundation and the National Science Foundation (BCS - 8915307). S.L.N. was supported by an Ethicon/Society of University Surgeons Research Fellowship. {\textquoteright} Presented at the Annual Meeting of the Association for Academic Surgery, Colorado Springs, Colorado, November 20-23, 1991.",

year = "1992",

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doi = "10.1016/0022-4804(92)90253-V",

language = "English (US)",

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pages = "549--557",

journal = "Journal of Surgical Research",

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AU - Shatford, Russell A.

AU - Nyberg, Scott L.

AU - Meier, Steven J.

AU - White, James G.

AU - Payne, William D.

AU - Hu, Wei Shou

AU - Cerra, Frank B.

N1 - Funding Information: 1 This research was supported in part by grants from the Whittaker Foundation and the National Science Foundation (BCS - 8915307). S.L.N. was supported by an Ethicon/Society of University Surgeons Research Fellowship. ’ Presented at the Annual Meeting of the Association for Academic Surgery, Colorado Springs, Colorado, November 20-23, 1991.

PY - 1992/12

Y1 - 1992/12

N2 - 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.

AB - 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.

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ER -

Hepatocyte function in a hollow fiber bioreactor: A potential bioartificial liver

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