Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis, Indiana.
Department of Anesthesiology and Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
Am J Physiol Cell Physiol. 2022 Jul 1;323(1):C1-C13. doi: 10.1152/ajpcell.00374.2021. Epub 2022 May 4.
The choroid plexus epithelium (CPe) forms a barrier between the cerebral blood supply and the cerebrospinal fluid (CSF), establishing the blood-CSF barrier (BCSFB). CSF is actively secreted by the CPe via tightly controlled processes involving multiple channels, transporters, and pumps. The importance of controlling CSF production and composition has been accentuated recently with an appreciation of CSF dysfunction in many pathologies. For mechanistic studies of CSF production, isolated CPe cell lines are valuable for the testing of hypotheses and potential drug targets. Although several continuous CPe cell lines have been described, none appear to have all the characteristics of the native epithelium and each must be used judiciously. The porcine choroid plexus-Riems (PCP-R) cell line forms a high-resistance monolayer characteristic of a barrier epithelium. Conservation of this phenotype is unusual among CPe cell lines, making this model useful for studies of the effects of infection, injury, and drugs on permeability. We have recently discovered that, although this line expresses many of the transporters expressed in the native tissue, some are mispolarized. As a result, inferences regarding fluid/electrolyte flux and the resultant CSF production should be pursued with caution. Furthermore, extended culture periods and changes in media composition result in significant morphological and functional variability. These studies provide a more detailed characterization of the PCP-R cell line concerning transporter expression, polarization, and functionality, as well as plasticity in culture, with the goal to provide the scientific community with information necessary to optimize future experiments with this model.
脉络丛上皮(CPe)在脑血液供应和脑脊液(CSF)之间形成屏障,建立了血脑屏障(BCSFB)。CSF 通过 CPe 通过多种通道、转运体和泵的紧密控制过程主动分泌。最近,人们越来越重视 CSF 功能障碍在许多病理中的作用,因此控制 CSF 产生和组成的重要性更加凸显。对于 CSF 产生的机制研究,分离的 CPe 细胞系对于测试假说和潜在药物靶点非常有价值。尽管已经描述了几种连续的 CPe 细胞系,但似乎没有一种具有天然上皮的所有特征,每种细胞系都必须谨慎使用。猪脉络丛-Riems(PCP-R)细胞系形成了具有屏障上皮特征的高电阻单层。这种表型的保守性在 CPe 细胞系中并不常见,这使得该模型对于研究感染、损伤和药物对通透性的影响非常有用。我们最近发现,尽管该细胞系表达了许多在天然组织中表达的转运体,但其中一些存在极化错误。因此,关于流体/电解质通量和由此产生的 CSF 产生的推论应该谨慎进行。此外,延长培养时间和培养基组成的变化会导致显著的形态和功能变异性。这些研究更详细地描述了 PCP-R 细胞系在转运体表达、极化和功能方面的特征,以及在培养中的可塑性,目的是为科学界提供必要的信息,以优化未来使用该模型的实验。