Department of Biomaterials Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.
Department of Cell Biology inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, University of Maastricht, Maastricht, The Netherlands.
J Tissue Eng Regen Med. 2018 Feb;12(2):e817-e827. doi: 10.1002/term.2387. Epub 2017 Jun 20.
Increasing incidence of renal pathology in the western world calls for innovative research for the development of cell-based therapies such as a bioartificial kidney (BAK) device. To fulfil the multitude of kidney functions, the core component of the BAK is a living membrane consisting of a tight kidney cell monolayer with preserved functional organic ion transporters cultured on a polymeric membrane surface. This membrane, on one side, is in contact with blood and therefore should have excellent blood compatibility, whereas the other side should facilitate functional monolayer formation. This work investigated the effect of membrane chemistry and surface topography on kidney epithelial cells to improve the formation of a functional monolayer. To achieve this, microtopographies were fabricated with high resolution and reproducibility on polystyrene films and on polyethersulfone-polyvinyl pyrrolidone (PES-PVP) porous membranes. A conditionally immortalized proximal tubule epithelial cell line (ciPTEC) was cultured on both, and subsequently, the cell morphology and monolayer formation were assessed. Our results showed that L-dopamine coating of the PES-PVP was sufficient to support ciPTEC monolayer formation. The polystyrene topographies with large features were able to align the cells in various patterns without significantly disruption of monolayer formation; however, the PES-PVP topographies with large features disrupted the monolayer. In contrast, the PES-PVP membranes with small features and with large spacing supported well the ciPTEC monolayer formation. In addition, the topographical PES-PVP membranes were compatible as a substrate membrane to measure organic cation transporter activity in Transwell® systems. Copyright © 2016 John Wiley & Sons, Ltd.
在西方世界，肾脏病理发病率不断上升，这就需要开展创新性研究，以开发细胞疗法，例如生物人工肾（BAK）设备。为了实现众多肾脏功能，BAK 的核心组件是一种由紧密的肾细胞单层组成的生物活性膜，该单层具有保留的功能性有机离子转运体，培养在聚合物膜表面上。该膜的一侧与血液接触，因此应具有出色的血液相容性，而另一侧应促进功能性单层的形成。这项工作研究了膜化学和表面形貌对肾上皮细胞的影响，以改善功能性单层的形成。为了实现这一目标，使用高分辨率和可重复性在聚苯乙烯膜和聚醚砜-聚乙烯吡咯烷酮（PES-PVP）多孔膜上制造了微观形貌。将条件永生化的近端肾小管上皮细胞系（ciPTEC）培养在这两种膜上，然后评估细胞形态和单层形成。我们的研究结果表明，PES-PVP 的 L-多巴胺涂层足以支持 ciPTEC 单层的形成。具有大特征的聚苯乙烯形貌能够以各种图案对齐细胞，而不会严重破坏单层的形成；然而，具有大特征的 PES-PVP 形貌会破坏单层。相比之下，具有小特征和大间距的 PES-PVP 膜能够很好地支持 ciPTEC 单层的形成。此外，具有形貌的 PES-PVP 膜作为基底膜是相容的，可在 Transwell®系统中测量有机阳离子转运体的活性。版权所有©2016 年 John Wiley & Sons, Ltd.
