A bioartificial liver device based on three-dimensional culture of genetically engineered hepatoma cells using hollow fibers

TY - JOUR

T1 - A bioartificial liver device based on three-dimensional culture of genetically engineered hepatoma cells using hollow fibers

AU - Fujii, Yusuke

AU - Higashi, Kengo

AU - Mizumoto, Hiroshi

AU - Kamihira, Masamichi

AU - Kajiwara, Toshihisa

N1 - Publisher Copyright: © 2020, Springer Nature B.V.

PY - 2020/4/1

Y1 - 2020/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85078921331&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85078921331&partnerID=8YFLogxK

U2 - 10.1007/s10616-020-00372-0

DO - 10.1007/s10616-020-00372-0

M3 - Article

AN - SCOPUS:85078921331

SN - 0920-9069

VL - 72

SP - 227

EP - 237

JO - Cytotechnology

JF - Cytotechnology

IS - 2

ER -