Angelow Susanne, Zeni Patrick, Galla Hans-Joachim
Institut für Biochemie, Westfälische Wilhelms-Universität Münster, Wilhelm-Klemm-Str. 2, 48149 Münster, Germany.
Adv Drug Deliv Rev. 2004 Oct 14;56(12):1859-73. doi: 10.1016/j.addr.2004.07.012.
The epithelial cells of the choroid plexus form the anatomical structure responsible for the blood-cerebrospinal fluid (CSF) barrier. Here we present our recent progress in the application of porcine choroid plexus epithelial cells in the investigation of permeability and transport properties of this tissue in vitro. Isolated cells are seeded on permeable supports where they grow to confluent monolayers. The cell differentiation is significantly increased under serum-free culture conditions, verifiable by an improvement of barrier properties and enhanced characteristics of the epithelial phenotype. We underline the importance of a tight model system for the investigation of transport processes by showing that permeability and transport properties critically depend on the electrical tightness of the monolayer. The mechanisms of vectorial transfer of micronutrients across the epithelial layer have been investigated in detail for ascorbic acid and myo-inositol transport. Additionally, we describe the transfer of organic anions and the expression of the corresponding transport proteins in vitro. The model system was applied to determine permeation rates of various drugs into the CSF. In conclusion our porcine in vitro model of the blood-CSF barrier provides a reliable system to study the transport characteristics of the choroid plexus epithelium and to probe the passage of drugs.
脉络丛上皮细胞构成了血脑屏障的解剖结构。在此,我们展示了猪脉络丛上皮细胞在体外研究该组织的通透性和转运特性方面的最新进展。将分离的细胞接种在可渗透支持物上,使其生长至汇合的单层。在无血清培养条件下,细胞分化显著增加,这可通过屏障特性的改善和上皮表型特征的增强得到验证。我们通过表明通透性和转运特性严重依赖于单层的电紧密性,强调了紧密模型系统在研究转运过程中的重要性。已针对抗坏血酸和肌醇转运详细研究了微量营养素跨上皮层的向量转运机制。此外,我们描述了有机阴离子的转运以及体外相应转运蛋白的表达。该模型系统用于确定各种药物进入脑脊液的渗透率。总之,我们的猪血脑屏障体外模型为研究脉络丛上皮细胞的转运特性和探测药物的通过提供了一个可靠的系统。