Open AccessA bioartificial liver device based on three-dimensional culture of genetically engineered hepatoma cells using hollow fibers
Author(s) -
Yusuke Fujii,
Katsumi Higashi,
Hiroshi Mizumoto,
Masamichi Kamihira,
Toshihisa Kajiwara
Publication year - 2020
Publication title -
cytotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.488
H-Index - 62
eISSN - 1573-0778
pISSN - 0920-9069
DOI - 10.1007/s10616-020-00372-0
Subject(s) - bioartificial liver device , hepa , albumin , hepatocyte , secretion , cell culture , doxycycline , chemistry , microbiology and biotechnology , biology , biochemistry , in vitro , filter (signal processing) , computer science , computer vision , genetics , antibiotics
The bioartificial liver (BAL) device is an extracorporeal liver support system incorporating living hepatocytes. A major problem in BAL device development is to obtain a high number of functional cells. In this study, we focused on a genetically engineered mouse hepatoma cell line, Hepa/8F5, in which elevated liver functions are induced via overexpression of liver-enriched transcription factors activated by doxycycline (Dox) addition. We applied a three-dimensional culture technique using hollow fibers (HFs) to Hepa/8F5 cells. Hepa/8F5 cells responded to Dox addition by reducing their proliferative activity and performing liver-specific functions of ammonia removal and albumin secretion. The functional activities of cells depended on the timing of Dox addition. We also found that Hepa/8F5 cells in the HF culture were highly functional in a low rather than high cell density environment. We further fabricated an HF-type bioreactor with immobilized Hepa/8F5 cells as a BAL device. Although ammonia removal activity of this BAL device was lower than that of the small-scale HF bundle, albumin secretion activity was slightly higher. These results indicated that the BAL device with immobilized Hepa/8F5 cells was highly functional with potential to show curative effects in liver failure treatment.