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Biomimetic urothelium
We have developed a new method for the in vitro cultivation of stratified, differentiated urothelial tissue, which mimics the functional properties of naturally occurring mammalian urothelium. The in vitro tissue has now also been adapted for use in 96 well plates making it suitable as an assay system for screening drug toxicity and efficacy.
Numerous attempts have been made over the last 20 years to produce an in vitro-generated urothelium, but to date the results have borne little resemblance to functional urothelium. Although urothelial cells have been successfully cultivated, there has been little or no stratification and differentiation into an organised tissue. Stratification and differentiation are important in natural urothelium, providing it with low permeability to molecules such as urea, ammonia, water and protons and also to large molecules such as dextrans, and an active transepithelial ion transport system.
Benefits
Functional urothelium possesses the following features:
- stratified morphology of basal, intermediate and superficial cells
- presence of uroplakin protein plaques on the apical surface of the membrane
- presence of tight junctions between the cells of the membrane
- spatially correct location of amiloride-sensitive sodium channels and basolateral expression of Na+ -K+ ATPase
- high transepithelial resistance
- low passive permeability to other small and large molecular weight species.
The tissue produced at York has demonstrated a high degree of differentiation and stratification, together with a number of functional properties, including high transepithelial electrical resistance and an active ion transport system.
It has the potential to provide a model for the study of both normal physiological and pathophysiological function, for the study of the action of pharmaceutical compounds as part of drug discovery programmes. Current methods include the use of either undifferentiated or tumour cell culture, neither of which is regarded as a good model for the natural tissue.
Applications
- A biomimetic urothelium based assay has application for the assessment of toxicity of a broad range of drugs and other chemicals including cosmetics, which may become concentrated in the human bladder.
- The assay will also be of use in the assessment of drug efficacy for pharmaceuticals designed to function in the human bladder
Investment Readiness Statement
We are keen to collaborate with pharmaceutical companies working in relevant drug discovery programmes in diseases of the bladder and urological system
IP status
The method for producing the stratified urothelium has been patented. Patents have been granted in the UK, Europe and Japan, and are filed for the US.