Scholarlink

<p>Scalable production of functional hepatocytes remains a major challenge for the development of in vitro liver models. Hepatoma-derived cells are attractive due to their proliferative capacity, but their typically low liver-specific functions limit both clinical and industrial applications. Here, we describe a heat-inducible hepatic cell line (hi-Hep), generated by overexpressing BRCA1-associated protein-1 (BAP1) in the human hepatoma-derived cell line HepG2/8F_HS. A transient heat stimulus (43&#xa0;°C, 30&#xa0;min) induced growth arrest and markedly enhanced liver-specific functions, including albumin secretion, ammonia clearance, and cytochrome P450 activity, surpassing those of both HepG2 and HepG2/8F_HS. Exploratory transcriptomic profiling revealed coordinated upregulation of DNA replication and biosynthetic pathways, consistent with a shift toward a metabolically active hepatic phenotype. In three-dimensional culture, hi-Hep organoids embedded in alginate–collagen hydrogels exhibited further enhanced detoxification capacity. These findings suggest that BAP1 overexpression may contribute to the enhancement of hepatic metabolic and detoxification functions in hepatoma-derived cells, supporting the potential utility of hi-Hep as a platform for bioartificial liver systems and drug testing models.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Engineered hepatic cells with stable expansion and heat-inducible liver function

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月6日

查看全文
  • Silas Habimana,
  • Hiroyuki Kitano,
  • Hirokazu Akiyama,
  • Yoshinori Kawabe,
  • Masamichi Kamihira

摘要

Scalable production of functional hepatocytes remains a major challenge for the development of in vitro liver models. Hepatoma-derived cells are attractive due to their proliferative capacity, but their typically low liver-specific functions limit both clinical and industrial applications. Here, we describe a heat-inducible hepatic cell line (hi-Hep), generated by overexpressing BRCA1-associated protein-1 (BAP1) in the human hepatoma-derived cell line HepG2/8F_HS. A transient heat stimulus (43 °C, 30 min) induced growth arrest and markedly enhanced liver-specific functions, including albumin secretion, ammonia clearance, and cytochrome P450 activity, surpassing those of both HepG2 and HepG2/8F_HS. Exploratory transcriptomic profiling revealed coordinated upregulation of DNA replication and biosynthetic pathways, consistent with a shift toward a metabolically active hepatic phenotype. In three-dimensional culture, hi-Hep organoids embedded in alginate–collagen hydrogels exhibited further enhanced detoxification capacity. These findings suggest that BAP1 overexpression may contribute to the enhancement of hepatic metabolic and detoxification functions in hepatoma-derived cells, supporting the potential utility of hi-Hep as a platform for bioartificial liver systems and drug testing models.