A bioartificial environment for kidney epithelial cells based on a supramolecular polymer basement membrane mimic and an organotypical culture system

B.B. Mollet, I.L.J. Bogaerts, G.C. van Almen, P.Y.W. Dankers

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)
1 Downloads (Pure)

Abstract

Renal applications in healthcare, such as renal replacement therapies and nephrotoxicity tests, could potentially benefit from bioartificial kidney membranes with fully differentiated and functional human tubular epithelial cells. A replacement of the natural environment of these cells is required to maintain and study cell functionality cell differentiation in vitro. Our approach was based on synthetic supramolecular biomaterials to mimic the natural basement membrane (BM) on which these cells grow and a bioreactor to provide the desired organotypical culture parameters. The BM mimics were constructed from ureidopyrimidinone (UPy)-functionalized polymer and bioactive peptides by electrospinning. The resultant membranes were shown to have a hierarchical fibrous BM-like structure consisting of self-assembled nanofibres within the electrospun microfibres. Human kidney-2 (HK-2) epithelial cells were cultured on the BM mimics under organotypical conditions in a custom-built bioreactor. The bioreactor facilitated in situ monitoring and functionality testing of the cultures. Cell viability and the integrity of the epithelial cell barrier were demonstrated inside the bioreactor by microscopy and transmembrane leakage of fluorescently labelled inulin, respectively. Furthermore, HK-2 cells maintained a polarized cell layer and showed modulation of both gene expression of membrane transporter proteins and metabolic activity of brush border enzymes when subjected to a continuous flow of culture medium inside the new bioreactor for 21days. These results demonstrated that both the culture and study of renal epithelial cells was facilitated by the bioartificial in vitro environment that is formed by synthetic supramolecular BM mimics in our custom-built bioreactor.

Original languageEnglish
Pages (from-to)1820-1834
Number of pages15
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume11
Issue number6
DOIs
Publication statusPublished - 1 Jun 2017

Keywords

  • Basement membrane mimic
  • Bioreactor
  • Flow culture
  • in vitro test
  • Kidney epithelial cell
  • Supramolecular biomaterial

Fingerprint Dive into the research topics of 'A bioartificial environment for kidney epithelial cells based on a supramolecular polymer basement membrane mimic and an organotypical culture system'. Together they form a unique fingerprint.

  • Cite this