Induction of zone-like liver function gradients in HepG2 cells by varying culture medium height
Induction of zone-like liver function gradients in HepG2 cells by varying culture medium height
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DOI：
10.1021/bp070308v
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发表时间：
2007-11-01
影响因子：
2.9
通讯作者：
Capitano, Adam T.
中科院分区：
文献类型：
--
作者：
Camp, James P.;Capitano, Adam T.
在大多数实验室规模的哺乳动物细胞培养中，氧气输送到培养细胞的主要模式是通过一层薄薄的培养基被动扩散，因此选择的培养基高度可能对氧敏感细胞类型的表型有显著影响。肝细胞的许多肝功能被认为受局部氧浓度的调控。体外毒理学家特别感兴趣的是，已知细胞色素P450解毒酶家族在低（静脉周围）氧浓度下优先由肝细胞表达。我们在12孔板中使用不同培养基高度的阵列，发现培养基高度对HepG2肝癌细胞色素P450 1A1解毒活性、葡萄糖代谢和细胞形态有显著影响。特别是，细胞色素P450活性在与静脉周围氧浓度相对应的中等高度表现出最大。这项工作表明，优化细胞培养性能并不总是与最大化氧气输送相同。
In most laboratory-scale mammalian cell cultures, the primary mode of oxygen delivery to cultured cells is by passive diffusion through a thin layer of culture medium, and the height of culture medium chosen may therefore have a significant effect on the phenotype of oxygen-sensitive cell types. Many of the liver functions performed by hepatocytes are thought to be regulated into zones by the local oxygen concentration; of particular interest to in vitro toxicologists, the cytochrome P450 family of detoxification enzymes is known to be preferentially expressed by hepatocytes at low (perivenous) oxygen concentrations. Using an array of different medium heights in a 12-well plate format, we show that the height of culture medium has a significant effect on cytochrome P450 1A1 detoxification activity, glucose metabolism, and cell morphology of HepG2 hepatocellular carcinoma cultures. In particular, cytochrome P450 activity exhibits a maximum at medium heights corresponding to perivenous oxygen concentrations. This work demonstrates that optimizing cell culture performance is not always the same as maximizing oxygen delivery.