Abstract
Hepatoma cells derived from liver carcinoma are a candidate cell source for bioartificial liver (BAL) systems due to their high proliferative capacity, although liver function of hepatoma cells is considerably low compared with primary hepatocytes. In our previous study, genetically engineered mouse hepatoma cells with inducible high liver function were established by transducing liver-enriched transcription factor (LETF) genes. In this study, we aimed to develop new gene-engineered human hepatoma cells, in which high liver functions are inducible by heat treatment. For this purpose, we constructed a gene expression system for eight LETF genes under control of tetracycline-dependent transactivator (tTA), and the system was introduced into the genome of HepG2-HSP cells, in which a tTA expression system induced by a heat-shock protein promoter with transcriptional amplification was introduced into HepG2 cells. Thus, the heat-inducible tTA promotes LETF genes to induce liver function. Upon the heat treatment of the cells (HepG2-HSP/8F) at 43°C for 30 min, liver functions such as albumin secretion and cytochrome P450 were significantly enhanced. The cells with heat-inducible liver function can be used as a new cell source for various hepatic studies including construction of BAL systems.
Highlights
The liver is the largest organ in the human body and has many functions that are essential to the maintenance of our lives
Several bioartificial liver (BAL) systems have been proposed to use for clinical application (Lee et al, 2016), development for practical use has not progressed mainly due to the lack of suitable cells to be loaded
The expression level of liver function in hepatoma cells is significantly low compared with primary hepatocytes
Summary
The liver is the largest organ in the human body and has many functions that are essential to the maintenance of our lives. Liver transplantation is the only effective treatment for acute and chronic liver failure (Neuberger, 2000), the shortage of donor organs is a serious problem. Cell transplantation and bioartificial liver (BAL) devices have been studied as treatments to complement and replace liver transplantation (Chamuleau et al, 2005). A BAL device is an extracorporeal support system in which functional hepatic cells are filled into a bioreactor. The hepatic cells metabolize xenobiotics and secret bioactive substances into the blood, and supporting liver function and promoting liver regeneration. Several BAL systems have been proposed to use for clinical application (Lee et al, 2016), development for practical use has not progressed mainly due to the lack of suitable cells to be loaded
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