具有稳定扩增和热诱导肝功能的工程肝细胞
Engineered hepatic cells with stable expansion and heat-inducible liver function.
摘要(中文译文)
功能性肝细胞的可规模化生产仍然是体外肝脏模型开发的一大挑战。肝癌来源的细胞因其增殖能力而具有吸引力，但其通常较低的肝脏特异性功能限制了临床和工业应用。在此，我们描述了一种热诱导型肝细胞系（hi-Hep），该细胞系通过在人肝癌来源细胞系HepG2/8F_HS中过表达BRCA1相关蛋白-1（BAP1）而构建。短暂的热刺激（43°C，30分钟）可诱导生长停滞并显著增强肝脏特异性功能，包括白蛋白分泌、氨清除和细胞色素P450活性，且超过HepG2和HepG2/8F_HS细胞。探索性转录组分析显示DNA复制和生物合成通路协同上调，与向代谢活跃的肝表型转变相一致。在三维培养中，包埋于海藻酸盐-胶原水凝胶中的hi-Hep类器官表现出进一步增强的解毒能力。这些发现表明，BAP1过表达可能有助于增强肝癌来源细胞的肝脏代谢和解毒功能，支持hi-Hep作为生物人工肝系统和药物测试模型平台的潜在应用价值。
Abstract
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.
如何引用
AMA
Silas Habimana, Hiroyuki Kitano, Hirokazu Akiyama, Yoshinori Kawabe, Masamichi Kamihira. Engineered hepatic cells with stable expansion and heat-inducible liver function.. Scientific reports. 2026; doi:10.1038/s41598-026-60521-x.
APA
Silas Habimana, Hiroyuki Kitano, Hirokazu Akiyama, Yoshinori Kawabe, Masamichi Kamihira (2026). Engineered hepatic cells with stable expansion and heat-inducible liver function.. Scientific reports. https://doi.org/10.1038/s41598-026-60521-x
GB/T 7714
Silas Habimana, Hiroyuki Kitano, Hirokazu Akiyama, Yoshinori Kawabe, Masamichi Kamihira. Engineered hepatic cells with stable expansion and heat-inducible liver function.[J]. Scientific reports, 2026 doi:10.1038/s41598-026-60521-x.
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