By the same authors

From the same journal

Biomimetic urothelial tissue models for the in vitro evaluation of barrier physiology and bladder drug efficacy

Research output: Contribution to journalArticlepeer-review

Published copy (DOI)

Author(s)

Department/unit(s)

Publication details

JournalMOLECULAR PHARMACEUTICS
DateE-pub ahead of print - 3 Apr 2014
DatePublished (current) - 7 Jul 2014
Issue number7
Volume11
Number of pages7
Pages (from-to)1964-70
Early online date3/04/14
Original languageEnglish

Abstract

The bladder is an important tissue in which to evaluate xenobiotic drug interactions and toxicities due to the concentration of parent drug and hepatic/enteric-derived metabolites in the urine as a result of renal excretion. Breaching of the barrier provided by the bladder epithelial lining (the urothelium) can expose the underlying tissues to urine and cause harmful effects (e.g., cystitis or cancer). Human urothelium is most commonly represented in vitro as immortalized or established cancer-derived cell lines, but the compromised ability of such cells to undergo differentiation and barrier formation means that nonimmortalized, normal human urothelial (NHU) cells provide a more relevant cell culture system. The impressive capacity for urothelial self-renewal in vivo can be harnessed in vitro to generate experimentally-useful quantities of NHU cells, which can subsequently be differentiated to form a functional or "biomimetic" urothelium. When seeded onto permeable membranes, these barrier-forming human urothelial tissue models enable the modeling of serum and luminal (intravesical) exposure to drugs and metabolites, thus supporting efficacy/toxicity assessments. Biomimetic human urothelial constructs provide a potential step along the preclinical trail and may support the extrapolation from rodent in vivo data to determine human relevance. Early evidence is beginning to demonstrate that human urothelium in vitro can provide information that supersedes conventional rodent studies, but further validation is needed to support widespread adoption.

    Research areas

  • urinary tract, Ureter, toxicology, pharmacology, drug delivery

Discover related content

Find related publications, people, projects, datasets and more using interactive charts.

View graph of relations