Abstract
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.
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Acknowledgements
We would like to thank Takahiro Ono (UNITIKA LTD.) for providing hollow fibers.
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This study was supported in part by a Grant-in-Aid for Scientific Research (C) (17K06928) from the Japan Society for the Promotion of Science.
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Fujii, Y., Higashi, K., Mizumoto, H. et al. A bioartificial liver device based on three-dimensional culture of genetically engineered hepatoma cells using hollow fibers. Cytotechnology 72, 227–237 (2020). https://doi.org/10.1007/s10616-020-00372-0
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DOI: https://doi.org/10.1007/s10616-020-00372-0