RRC ID 12418
著者 Fukuda J, Okamura K, Ishihara K, Mizumoto H, Nakazawa K, Ijima H, Kajiwara T, Funatsu K.
タイトル Differentiation effects by the combination of spheroid formation and sodium butyrate treatment in human hepatoblastoma cell line (Hep G2): a possible cell source for hybrid artificial liver.
ジャーナル Cell Transplant
Abstract The aim of this study was to investigate the feasibility of human hepatoblastoma cell line (Hep G2), which differentiates by spheroid formation, and treatment with sodium butyrate (SB) as a cell source for hybrid artificial liver (HAL). Hep G2 spontaneously formed spheroids in polyurethane foam (PUF) within 3 days of culture and restored weak ammonia removal activity. Treatment with SB, which is a histone deacetylase inhibitor, further increased the ammonia removal activity of Hep G2 spheroids in a concentration-dependent manner. The activation of ornithine transcarbamylase--a urea cycle enzyme--was significantly related to the upregulation of ammonia removal by spheroid formation, but scarcely contributed to the further upregulation following SB treatment. In contrast with ammonia removal, treatment with SB reduced the albumin secretion of Hep G2 spheroids in a concentration-dependent manner. In the PUF-HAL module in a circulation culture, the ammonia removal rate and albumin secretion rate (per unit volume of the module) of Hep G2 spheroids treated with 5 mM SB were almost the same as those of primary porcine hepatocyte spheroids. These results suggest that simultaneous use of spheroid formation and SB treatment in Hep G2 is beneficial in enhancing the functions of human hepatocytes with potential applications in regenerative medicine and drug screening.
巻・号 14(10)
ページ 819-27
公開日 2005-1-1
DOI 10.3727/000000005783982503
PMID 16454356
MeSH Albumins / metabolism Ammonia / metabolism Animals Butyrates / pharmacology* Cell Line, Tumor Cell Proliferation / drug effects Enzyme Activation / physiology Female Fibrinogen / metabolism Gene Expression Regulation, Enzymologic / drug effects Gene Expression Regulation, Enzymologic / physiology Hepatoblastoma / metabolism Hepatoblastoma / pathology* Hepatoblastoma / physiopathology Hepatocytes / drug effects Hepatocytes / physiology Histone Deacetylase Inhibitors Humans Lactic Acid / metabolism Liver Neoplasms / metabolism Liver Neoplasms / pathology* Liver Neoplasms / physiopathology Liver, Artificial* Ornithine Carbamoyltransferase / genetics Ornithine Carbamoyltransferase / physiology Polyurethanes Reverse Transcriptase Polymerase Chain Reaction Spheroids, Cellular / drug effects Spheroids, Cellular / physiology* Spheroids, Cellular / transplantation
IF 3.341
引用数 15
WOS 分野 TRANSPLANTATION MEDICINE, RESEARCH & EXPERIMENTAL CELL & TISSUE ENGINEERING
リソース情報
ヒト・動物細胞