Institute of Bioengineering and Nanotechnology, The Nanos, Singapore, Singapore.
Biomaterials. 2011 Dec;32(34):8806-15. doi: 10.1016/j.biomaterials.2011.08.030. Epub 2011 Aug 27.
Bioartificial kidneys (BAKs) containing human primary renal proximal tubule cells (HPTCs) have been applied in clinical trials. The results were encouraging, but also showed that more research is required. Animal cells or cell lines are not suitable for clinical applications, but have been mainly used in studies on BAK development as large numbers of such cells could be easily obtained. It is difficult to predict HPTC performance based on data obtained with other cell types. To enable more extensive studies on HPTCs, we have developed a bioreactor containing single hollow fiber membranes that requires relatively small amounts of cells. Special hollow fiber membranes with the skin layer on the outer surface and consisting of polyethersulfone/polyvinylpyrrolidone were developed. The results suggested that such hollow fiber membranes were more suitable for the bioreactor unit of BAKs than membranes with an inner skin layer. An HPTC-compatible double coating was applied to the insides of the hollow fiber membranes, which sustained the formation of functional epithelia under bioreactor conditions. Nevertheless, the state of differentiation of the primary human cells remained a critical issue and should be further addressed. The bioreactor system described here will facilitate further studies on the relevant human cell type.
生物人工肾(BAK)中含有人类原代肾近端小管细胞(HPTCs),已应用于临床试验。结果令人鼓舞,但也表明需要进一步研究。动物细胞或细胞系不适合临床应用,但主要用于 BAK 开发研究,因为可以很容易地获得大量此类细胞。根据其他细胞类型获得的数据来预测 HPTC 的性能具有一定难度。为了能够对 HPTC 进行更广泛的研究,我们开发了一种含有单个中空纤维膜的生物反应器,该生物反应器需要相对较少的细胞。开发了具有外层表皮的特殊中空纤维膜,由聚醚砜/聚乙烯吡咯烷酮组成。结果表明,与具有内皮层的膜相比,这种中空纤维膜更适合 BAK 的生物反应器单元。将一种与人肾细胞相容的双层涂层应用于中空纤维膜的内部,在生物反应器条件下维持了功能性上皮的形成。然而,原代人细胞的分化状态仍然是一个关键问题,需要进一步解决。本文所述的生物反应器系统将有助于对相关人类细胞类型的进一步研究。