%0 Journal Article
%T A Fibrin-Based Tissue-Engineered Renal Proximal Tubule for Bioartificial Kidney Devices: Development, Characterization and In Vitro Transport Study
%A Chee Ping Ng
%A Yuhang Zhuang
%A Alex Wei Haw Lin
%A Jeremy Choon Meng Teo
%J International Journal of Tissue Engineering
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/319476
%X A bioartificial renal proximal tubule is successfully engineered as a first step towards a bioartificial kidney for improved renal substitution therapy. To engineer the tubule, a tunable hollow fiber membrane with an exterior skin layer that provides immunoprotection for the cells from extracapillary blood flow and a coarse inner surface that facilitates a hydrogel coating for cell attachment was embedded in a ¡°lab-on-a-chip¡± model for the small-scale exploratory testing under flow conditions. Fibrin was coated onto the inner surface of the hollow fiber, and human renal proximal tubule epithelial cells were then seeded. Using this model, we successfully cultured a confluent monolayer, as ascertained by immunofluorescence staining for ZO-1 tight junctions and other proximal tubule markers, scanning electron microscopy, and FITC-inulin recovery studies. Furthermore, the inulin studies, combined with the creatinine and glucose transport profiles, suggested that the confluent monolayer exhibits functional transport capabilities. The novel approaches here may eventually improve current renal substitution technology for renal failure patients. 1. Introduction Hemodialysis has been widely used to treat patients suffering from end-stage renal failure. With hemodialysis, millions of renal failure patients in the world have not only survived, but are also able to successfully perform certain levels of social activities and functions. However, hemodialysis is still inefficient as a renal replacement therapy. It only provides intermittent blood filtration and is unable to replicate the important absorptive, metabolic, endocrine, and immunological functions of the natural kidney. To overcome such limitations, Aebischer et al. first proposed the concept of a bioartificial kidney that incorporates living epithelial cells of the kidney proximal tubule for the selective transport of water and solutes across the cell-attached membranes [1, 2]. Humes et al. have developed a bioartificial renal tubule assist device (RAD) using commercial hemodialysis hollow fiber membranes based on this concept [3¨C6] and conducted clinical trials on 10 to 40 patients with acute renal failure; encouraging results were reported [7, 8]. Saito et al. also developed a bioartificial renal tubule device (BRTD) with a capacity of treating 10£¿L of ultrafiltrate per day. Using proximal tubular epithelial cells in conjunction with continuous hemofiltration, the BRTD offers a potential wearable, continuous renal replacement therapy for patients with chronic renal failure [9¨C14]. In the development of
%U http://www.hindawi.com/journals/ijte/2013/319476/